Recent Submissions

  • Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland.

    Ingimarsson, Oddur; MacCabe, James H; Haraldsson, Magnús; Jónsdóttir, Halldóra; Sigurdsson, Engilbert; 1 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland. 2 Landspitali University Hospital, Mental Health Services, Hringbraut, 101, Reykjavik, Iceland. 3 Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, Kings College, London, UK. 4National Psychosis Unit, Bethlem Royal Hospital, South London and Maudsley NHS Foundation Trust, London, UK. 5 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland. 6 Landspitali University Hospital, Mental Health Services, Hringbraut, 101, Reykjavik, Iceland. (BioMed Central, 2016-12-12)
    Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia.
  • Biomarkers defining the metabolic age of red blood cells during cold storage.

    Paglia, Giuseppe; D'Alessandro, Angelo; Rolfsson, Óttar; Sigurjónsson, Ólafur E; Bordbar, Aarash; Palsson, Sirus; Nemkov, Travis; Hansen, Kirk C; Gudmundsson, Sveinn; Palsson, Bernhard O; [ 1 ] European Acad Bozen Bolzano, Ctr Biomed, Via Galvani 31, I-39100 Bolzano, Italy [ 2 ] Univ Colorado Denver, Sch Med, Dept Biochem & Mol Genet, Aurora, CO USA [ 3 ] Univ Iceland, Ctr Syst Biol, Reykjavik, Iceland [ 4 ] Landspitali Univ Hosp, Blood Bank, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 5 ] Reykjavik Unvers, Sch Sci & Engn, Reykjavik, Iceland [ 6 ] Sinopia Biosci, San Diego, CA USA (Amer Soc Hematology, 2016-09-29)
    Metabolomic investigations of packed red blood cells (RBCs) stored under refrigerated conditions in saline adenine glucose mannitol (SAGM) additives have revealed the presence of 3 distinct metabolic phases, occurring on days 0-10, 10-18, and after day 18 of storage. Here we used receiving operating characteristics curve analysis to identify biomarkers that can differentiate between the 3 metabolic states. We first recruited 24 donors and analyzed 308 samples coming from RBC concentrates stored in SAGM and additive solution 3. We found that 8 extracellular compounds (lactic acid, nicotinamide, 5-oxoproline, xanthine, hypoxanthine, glucose, malic acid, and adenine) form the basis for an accurate classification/regression model and are able to differentiate among the metabolic phases. This model was then validated by analyzing an additional 49 samples obtained by preparing 7 new RBC concentrates in SAGM. Despite the technical variability associated with RBC processing strategies, verification of these markers was independently confirmed in 2 separate laboratories with different analytical setups and different sample sets. The 8 compounds proposed here highly correlate with the metabolic age of packed RBCs, and can be prospectively validated as biomarkers of the RBC metabolic lesion.
  • Convergent validity of the interRAI-HC for societal costs estimates in comparison with the RUD Lite instrument in community dwelling older adults.

    van Lier, Lisanne I; van der Roest, Henriëtte G; van Hout, Hein P J; van Eenoo, Liza; Declercq, Anja; Garms-Homolová, Vjenka; Onder, Graziano; Finne-Soveri, Harriet; Jónsson, Pálmi V; Hertogh, Cees M P M; Bosmans, Judith E; 1Department of General Practice and Elderly Care Medicine and EMGO+ Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands. 2Department of General Practice and Elderly Care Medicine and EMGO+ Institute for Health and Care Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands. 3LUCAS, Centre for Care Research and Consultancy KU Leuven (University of Leuven), Minderbroederstraat 8, box 5310, B-3000, Leuven, Belgium. 4HTW Berlin, FB III-Economics, Treskowallee 8, D-10318, Berlin, Germany. 5Department of Geriatrics, Università Cattolica del Sacro, Largo F. Vito 1, 00168, Rome, Italy. 6Department of Wellbeing, National Institute for Health and Wellbeing, P.O. BOX 30, FI-00271, Helsinki, Finland. 7Department of Geriatrics, Landspitali National University Hospital and Faculty of Medicine, University of Iceland, Landakot, 101, Reykjavik, Iceland. 8Department of Health Sciences and EMGO+ Institute of Health and Care Research, Faculty of Earth and Life Sciences, VU University, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands. (BioMed Central, 2016)
    The interRAI-Home Care (interRAI-HC) instrument is commonly used in routine care to assess care and service needs, resource utilisation and health outcomes of community dwelling home care clients. Potentially, the interRAI-HC can also be used to calculate societal costs in economic evaluations. The purpose of this study was to assess the convergent validity of the interRAI-HC instrument in comparison with the RUD Lite instrument for the calculation of societal costs among care-dependent community dwelling older adults.
  • Variations in rates of severe perineal tears and episiotomies in 20 European countries: a study based on routine national data in Euro-Peristat Project.

    Blondel, Béatrice; Alexander, Sophie; Bjarnadóttir, Ragnheiður I; Gissler, Mika; Langhoff-Roos, Jens; Novak-Antolič, Živa; Prunet, Caroline; Zhang, Wei-Hong; Hindori-Mohangoo, Ashna D; Zeitlin, Jennifer; 1INSERM UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (Epopé), Center for Epidemiology and Statistics Sorbonne Paris Cité, DHU Risks in pregnancy, Paris Descartes University, Paris, France. 2Perinatal Epidemiology and Reproductive Health Unit, Epidemiology, Biostatistics and Clinical Research Centre, School of Public Health, Free University of Brussels, Brussels, Belgium. 3Landspitali University Hospital, Reykjavik, Iceland. 4THL National Institute for Health and Welfare, Helsinki, Finland. 5Obstetrics Clinic, Rigshospitalet University Hospital, Copenhagen, Denmark. 6Medical Faculty, Ljubljana University, Ljubljana, Slovenia. 7Department of Child Health, TNO Netherlands Organization for Applied Scientific Research, Leiden, the Netherlands. (Wiley, 2016-07)
    Rates of severe perineal tears and episiotomies are indicators of obstetrical quality of care, but their use for international comparisons is complicated by difficulties with accurate ascertainment of tears and uncertainties regarding the optimal rate of episiotomies. We compared rates of severe perineal tears and episiotomies in European countries and analysed the association between these two indicators.
  • A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis.

    Rivas, Manuel A; Graham, Daniel; Sulem, Patrick; Stevens, Christine; Desch, A Nicole; Goyette, Philippe; Gudbjartsson, Daniel; Jonsdottir, Ingileif; Thorsteinsdottir, Unnur; Degenhardt, Frauke; Mucha, Sören; Kurki, Mitja I; Li, Dalin; D'Amato, Mauro; Annese, Vito; Vermeire, Severine; Weersma, Rinse K; Halfvarson, Jonas; Paavola-Sakki, Paulina; Lappalainen, Maarit; Lek, Monkol; Cummings, Beryl; Tukiainen, Taru; Haritunians, Talin; Halme, Leena; Koskinen, Lotta L E; Ananthakrishnan, Ashwin N; Luo, Yang; Heap, Graham A; Visschedijk, Marijn C; MacArthur, Daniel G; Neale, Benjamin M; Ahmad, Tariq; Anderson, Carl A; Brant, Steven R; Duerr, Richard H; Silverberg, Mark S; Cho, Judy H; Palotie, Aarno; Saavalainen, Päivi; Kontula, Kimmo; Färkkilä, Martti; McGovern, Dermot P B; Franke, Andre; Stefansson, Kari; Rioux, John D; Xavier, Ramnik J; Daly, Mark J; Barrett, J; de Lane, K; Edwards, C; Hart, A; Hawkey, C; Jostins, L; Kennedy, N; Lamb, C; Lee, J; Lees, C; Mansfield, J; Mathew, C; Mowatt, C; Newman, B; Nimmo, E; Parkes, M; Pollard, M; Prescott, N; Randall, J; Rice, D; Satsangi, J; Simmons, A; Tremelling, M; Uhlig, H; Wilson, D; Abraham, C; Achkar, J P; Bitton, A; Boucher, G; Croitoru, K; Fleshner, P; Glas, J; Kugathasan, S; Limbergen, J V; Milgrom, R; Proctor, D; Regueiro, M; Schumm, P L; Sharma, Y; Stempak, J M; Targan, S R; Wang, M H; Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA deCODE Genetics, Amgen Inc., 101 Reykjavik, Iceland Research Center, Montreal Heart Institute, Montréal, Québec, Canada H1T1C8 School of Engineering and Natural Sciences, University of Iceland, 101 Reykjavik, Iceland Department of Immunology, Landspitali, the National University Hospital of Iceland, 101 Reykjavik, Iceland Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California 90048 USA Department of Biosciences and Nutrition, Karolinska Institutet, 14183 Stockholm, Sweden BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, 48903 Bilbao, Spain Unit of Gastroenterology, Istituto di Ricovero e Cura a Carattere Scientifico-Casa Sollievo della Sofferenza (IRCCS-CSS) Hospital, 71013 San Giovanni Rotondo, Italy Strutture Organizzative Dipartimentali (SOD) Gastroenterologia 2, Azienda Ospedaliero Universitaria (AOU) Careggi, 50134 Florence, Italy Department of Clinical and Experimental Medicine, Translational Research in GastroIntestinal Disorders (TARGID), Katholieke Universiteit (KU) Leuven, Leuven 3000, Belgium Division of Gastroenterology, University Hospital Gasthuisberg, BE-3000 Leuven, Belgium Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, 9713 GZ Groningen, The Netherlands Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, SE 701 82 Örebro, Sweden Department of Medicine, University of Helsinki, 00100 Helsinki, Finland Helsinki University Hospital, 00100 Helsinki, Finland Clinic of Gastroenterology, Helsinki University Hospital, 00100 Helsinki, Finland Research Programs Unit, Immunobiology, and Department of Medical and Clinical Genetics, University of Helsinki, 00014 Helsinki, Finland Department of Transplantation and Liver Surgery, University of Helsinki, 00100 Helsinki, Finland Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, 00100 Helsinki, Finland Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts 02114, USA Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK IBD Pharmacogenetics, Royal Devon and Exeter NHS Trust, Exeter EX2 5DW, UK Graham A. Heap Peninsula College of Medicine and Dentistry, Exeter PL6 8BU, UK Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, 21205, USA Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, 21205, USA Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania 15261, USA Department of Medicine, Inflammatory Bowel Disease Centre, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5 Department of Genetics, Yale School of Medicine, New Haven, Connecticut 06510, USA Institute for Molecular Medicine Finland, University of Helsinki, 00100 Helsinki, Finland Massachusetts General Hospital, Center for Human Genetic Research, Psychiatric and Neurodevelopmental Genetics Unit, Boston, Massachusetts 02114, USA Research Programs Unit, Immunobiology, University of Helsinki, 00100 Helsinki, Finland Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada H3T 1J4 Department of Gastroenterology, Torbay Hospital, Devon, UK Department of Medicine, St. Mark’s Hospital, Middlesex, UK Nottingham Digestive Disease Centre, Queens Medical Centre, Nottingham, UK Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, UK Christ Church, University of Oxford, Oxford, UK Gastrointestinal Unit, Wester General Hospital, University of Edinburgh, Edinburgh, UK Newcastle University, Newcastle upon Tyne, UK Inflammatory Bowel Disease Research Group, Addenbrooke’s Hospital, Cambridge, UK Department of Medical and Molecular Genetics, Guy’s Hospital, London, UK Department of Medical and Molecular Genetics, King’s College London School of Medicine, Guy’s Hospital, London, UK Department of Medicine, Ninewells Hospital and Medical School, Dundee, UK Genetic Medicine, Manchester Academic Health Science Centre, Manchester, UK The Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK Translational Gastroenterology Unit, John Radcliffe Hospital, University of Oxford, Oxford, UK Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK Gastroenterology & General Medicine, Norfolk and Norwich University Hospital, Norwich, UK Translational Gastroenterology Unit and the Department of Pediatrics, University of Oxford, Oxford, UK Pediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, UK Child Life and Health, University of Edinburgh, Edinburgh, UK Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA Division of Gastroenterology, Royal Victoria Hospital, Montréal, Québec, Canada Inflammatory Bowel Disease Group, Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA Division of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA (Nature, 2016)
    Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.
  • Clozapine treatment and discontinuation in Iceland: A national longitudinal study using electronic patient records.

    Ingimarsson, Oddur; MacCabe, James H; Haraldsson, Magnús; Jónsdóttir, Halldóra; Sigurdsson, Engilbert; [ 1 ] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland [ 2 ] Landspitali Univ Hosp, Mental Hlth Serv, IS-101 Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 3 ] Kings Coll London, London WC2R 2LS, England [ 4 ] South London & Maudsley NHS Fdn Trust, Bethlem Royal Hosp, Natl Psychosis Unit, London, England (Taylor & Francis Ltd, 2016-08)
    Clozapine is the only drug approved for treatment-resistant schizophrenia. There is evidence that clozapine is underutilized.
  • Acute phase inflammation is characterized by rapid changes in plasma/peritoneal fluid N-glycosylation in mice.

    Rombouts, Yoann; Jónasdóttir, Hulda S; Hipgrave Ederveen, Agnes L; Reiding, Karli R; Jansen, Bas C; Freysdottir, Jona; Hardardottir, Ingibjörg; Ioan-Facsinay, Andreea; Giera, Martin; Wuhrer, Manfred; [ 1 ] Leiden Univ, Med Ctr, Ctr Prote & Metab, Leiden, Netherlands [ 2 ] Leiden Univ, Dept Rheumatol, Med Ctr, Leiden, Netherlands [ 3 ] Univ Toulouse, CNRS, UPS, Inst Pharmacol & Biol Struct, Toulouse, France [ 4 ] Univ Iceland, Fac Med, Biomed Ctr, Sch Hlth Sci, Reykjavik, Iceland [ 5 ] Landspitali Natl Univ Hosp Iceland, Dept Immunol, Reykjavik, Iceland [ 6 ] Landspitali Natl Univ Hosp Iceland, Ctr Rheumatol Res, Reykjavik, Iceland [ 7 ] Vrije Univ Amsterdam, Div BioAnalyt Chem, Amsterdam, Netherlands (Springer, 2016-06)
    Murine zymosan-induced peritonitis is a widely used model for studying the molecular and cellular events responsible for the initiation, persistence and/or resolution of inflammation. Among these events, it is becoming increasingly evident that changes in glycosylation of proteins, especially in the plasma and at the site of inflammation, play an important role in the inflammatory response. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)-based glycosylation profiling, we investigated the qualitative and quantitative effect of zymosan-induced peritonitis on N-glycosylation in mouse plasma and peritoneal fluid. Our results show that both N-glycomes exhibit highly similar glycosylation patterns, consisting mainly of diantennary and triantennary complex type N-glycans with high levels (>95 %) of galactosylation and sialylation (mostly NeuGc) and a medium degree of core fucosylation (30 %). Moreover, MS/MS structural analysis, assisted by linkage-specific derivatization of sialic acids, revealed the presence of O-acetylated sialic acids as well as disialylated antennae ("branching sialylation") characterized by the presence of α2-6-linked NeuGc on the GlcNAc of the NeuGcα2-3-Galβ1-3-GlcNAc terminal motif. A significant decrease of (core) fucosylation together with an increase of both α2-3-linked NeuGc and "branching sialylation" were observed in N-glycomes of mice challenged with zymosan, but not in control mice injected with PBS. Importantly, substantial changes in glycosylation were already observed 12 h after induction of peritonitis, thereby demonstrating an unexpected velocity of the biological mechanisms involved.
  • Substantial between-country differences in organising community care for older people in Europe-a review.

    Van Eenoo, Liza; Declercq, Anja; Onder, Graziano; Finne-Soveri, Harriet; Garms-Homolová, Vjenka; Jónsson, Pálmi V; Dix, Olivia H M; Smit, Johannes H; van Hout, Hein P J; van der Roest, Henriëtte G; [ 1 ] KU Leuven Univ Leuven, LUCAS, Leuven, Belgium [ 2 ] Univ Cattolica Sacro Cuore, Ctr Med Invecchiamento, Dept Geriatr, Rome, Italy [ 3 ] Natl Inst Hlth & Welf, Aging & Serv, Helsinki, Finland [ 4 ] Hsch Techn & Wirtschaft Berlin, Dept Econ & Law 3, Berlin, Germany [ 5 ] Univ Iceland, Landspitali Univ Hosp, Iceland Gerontol Res Inst, Fac Med, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital     University of Iceland [ 6 ] European Hlth Management Assoc, Cork, Ireland [ 7 ] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands [ 8 ] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands [ 9 ] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Dept Gen Practice & Elderly Care Med, Amsterdam, Netherlands (Oxford Univ Press, 2016-04)
    The European population is aging. The main drivers of public spending on health care for people of 65 years and older are hospital admission and admission to long-term care facilities. High quality community care can be a cost-effective and quality solution to respond to the impact of ageing populations on health-care systems. It is unclear how well countries are equipped to provide affordable and quality community care. The aim of this article is to describe and compare community care delivery with care-dependent older people in Europe. 
  • No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer.

    Hollestelle, Antoinette; van der Baan, Frederieke H; Berchuck, Andrew; Johnatty, Sharon E; Aben, Katja K; Agnarsson, Bjarni A; Aittomäki, Kristiina; Alducci, Elisa; Andrulis, Irene L; Anton-Culver, Hoda; Antonenkova, Natalia N; van Altena, Anne M; Van Asperen, C J; van den Berg, David; van den Ouweland, Ans M W; van Doorn, Helena C; Goodman, Marc T; Van Nieuwenhuysen, Els; van Rensburg, Elizabeth J; Vergote, Ignace; Mai, Phuong L; Poppe, Bruce; Bojesen, Anders; Verhoef, Senno; Vierkant, Robert A; Vijai, Joseph; Vitonis, Allison F; von Wachenfeldt, Anna; Walsh, Christine; Gore, Martin; Wang, Qin; Wang-Gohrke, Shan; Pylkäs, Katri; Balleine, Rosemary; Wappenschmidt, Barbara; Weischer, Maren; Bojesen, Stig E; Weitzel, Jeffrey N; Weltens, Caroline; Wentzensen, Nicolas; Whittemore, Alice S; Wilkens, Lynne R; Greene, Mark H; Radice, Paolo; Winqvist, Robert; Fridley, Brooke L; Wu, Anna H; Wu, Xifeng; Yang, Hannah P; Zaffaroni, Daniela; Bolla, Manjeet K; Pilar Zamora, M; Zheng, Wei; Ziogas, Argyrios; Ramus, Susan J; Chenevix-Trench, Georgia; Grip, Mervi; Mannermaa, Arto; Pharoah, Paul D P; Rookus, Matti A; Hooning, Maartje J; Goode, Ellen L; Bonanni, Bernardo; Brand, Judith S; Brauch, Hiltrud; Rebbeck, Timothy R; Brenner, Hermann; Brinton, Louise; Brooks-Wilson, Angela; Margolin, Sara; Gronwald, Jacek; Bruinsma, Fiona; Brunet, Joan; Brüning, Thomas; Budzilowska, Agnieszka; Bunker, Clareann H; Berger, Andreas; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S; Caligo, Maria A; Mariette, Frederique; Campbell, Ian; Gschwantler Kaulich, Daphne; Carter, Jonathan; Chang-Claude, Jenny; Chanock, Stephen J; Reed, Malcolm W R; Claes, Kathleen B M; Collée, J Margriet; Cook, Linda S; Couch, Fergus J; Cox, Angela; Marme, Frederik; Cramer, Daniel; Cross, Simon S; Apicella, Carmel; Cunningham, Julie M; Rennert, Gad; Cybulski, Cezary; Czene, Kamila; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; de la Hoya, Miguel; Martens, John W M; deFazio, Anna; Dennis, Joseph; Devilee, Peter; Risch, Harvey A; Guénel, Pascal; Dicks, Ed M; Diez, Orland; Doherty, Jennifer A; Domchek, Susan M; Dorfling, Cecilia M; Dörk, Thilo; Massuger, Leon F A G; Silva, Isabel Dos Santos; du Bois, Andreas; Gentry-Maharaj, Aleksandra; Dumont, Martine; Dunning, Alison M; Guzman, Starr R; Duran, Mercedes; Easton, Douglas F; Eccles, Diana; Edwards, Robert P; Ehrencrona, Hans; Maugard, Christine; Ejlertsen, Bent; Lindblom, Annika; Ekici, Arif B; Ellis, Steve D; Engel, Christoph; Eriksson, Mikael; Haeberle, Lothar; Fasching, Peter A; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Mazoyer, Sylvie; Robson, Mark; Fletcher, Olivia; Fontaine, Annette; Fortuzzi, Stefano; Fostira, Florentia; Haiman, Christopher A; Hall, Per; Halverson, Sandra L; Hamann, Ute; Hansen, Thomas V O; Harter, Philipp; Rodriguez, Gustavo C; McGuffog, Lesley; Hartikainen, Jaana M; Arndt, Volker; Healey, Sue; Hein, Alexander; Heitz, Florian; Henderson, Brian E; Herzog, Josef; T Hildebrandt, Michelle A; Høgdall, Claus K; Romero, Atocha; Høgdall, Estrid; McGuire, Valerie; Hogervorst, Frans B L; Hopper, John L; Arnold, Norbert; Humphreys, Keith; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Jakubowska, Anna; Rossing, Mary Anne; Janavicius, Ramunas; Jaworska, Katarzyna; Friebel, Tara; Jensen, Allan; Jensen, Uffe Birk; Johnson, Nichola; Arun, Banu K; Jukkola-Vuorinen, Arja; Kabisch, Maria; Karlan, Beth Y; Rothstein, Joseph H; Kataja, Vesa; Kauff, Noah; Kelemen, Linda E; Bandera, Elisa V; Kerin, Michael J; Kiemeney, Lambertus A; Kjaer, Susanne K; Knight, Julia A; Arver, Brita; Knol-Bout, Jacoba P; Rudolph, Anja; Konstantopoulou, Irene; Kosma, Veli-Matti; Krakstad, Camilla; Kristensen, Vessela; McLean, Catriona; Kuchenbaecker, Karoline B; Kupryjanczyk, Jolanta; Laitman, Yael; Lambrechts, Diether; Lambrechts, Sandrina; Runnebaum, Ingo; Ashworth, Alan; Larson, Melissa C; Lasa, Adriana; Laurent-Puig, Pierre; Lazaro, Conxi; McNeish, Iain; Le, Nhu D; Le Marchand, Loic; Leminen, Arto; Lester, Jenny; Berger, Raanan; Levine, Douglas A; Li, Jingmei; Baglietto, Laura; Liang, Dong; Meindl, Alfons; Menegaux, Florence; Menéndez, Primitiva; Menkiszak, Janusz; Menon, Usha; Mensenkamp, Arjen R; Salani, Ritu; Miller, Nicola; Friedman, Eitan; Milne, Roger L; Barrowdale, Daniel; Modugno, Francesmary; Montagna, Marco; Moysich, Kirsten B; Müller, Heiko; Mulligan, Anna Marie; Muranen, Taru A; Salvesen, Helga B; Narod, Steven A; Nathanson, Katherine L; Friel, Grace; Ness, Roberta B; Neuhausen, Susan L; Bean, Yukie T; Nevanlinna, Heli; Neven, Patrick; Nielsen, Finn C; Nielsen, Sune F; Lindor, Noralane; Nordestgaard, Børge G; Nussbaum, Robert L; Odunsi, Kunle; Frost, Debra; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Beckmann, Lars; Olson, Janet E; Olson, Sara H; Gerdes, Anne-Marie; Oosterwijk, Jan C; Orlow, Irene; Orr, Nick; Orsulic, Sandra; Garber, Judy; Osorio, Ana; Ottini, Laura; Paul, James; Pearce, Celeste L; Beckmann, Matthias W; Sawyer, Elinor J; Pedersen, Inge Sokilde; Peissel, Bernard; Pejovic, Tanja; Pelttari, Liisa M; Perkins, Jo; García-Closas, Montserrat; Permuth-Wey, Jenny; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M; Schildkraut, Joellen M; Phillips, Kelly-Anne; Benitez, Javier; Piedmonte, Marion; Pike, Malcolm C; Platte, Radka; Plisiecka-Halasa, Joanna; Gayther, Simon A; Poole, Elizabeth M; Schmidt, Marjanka K; Schmutzler, Rita K; Schneeweiss, Andreas; Schoemaker, Minouk J; Schrauder, Michael G; Schumacher, Fredrick; Beuselinck, Benoit; Lissowska, Jolanta; Schwaab, Ira; Antoniou, Antonis C; Scuvera, Giulietta; Sellers, Thomas A; Severi, Gianluca; Seynaeve, Caroline M; Shah, Mitul; Shrubsole, Martha; Siddiqui, Nadeem; Sieh, Weiva; Long, Jirong; Simard, Jacques; Bisogna, Maria; Giles, Graham G; Singer, Christian F; Sinilnikova, Olga M; Smeets, Dominiek; Sohn, Christof; Soller, Maria; Song, Honglin; Soucy, Penny; Lu, Karen H; Southey, Melissa C; Stegmaier, Christa; Stoppa-Lyonnet, Dominique; Glasspool, Rosalind; Bjorge, Line; Sucheston, Lara; Swerdlow, Anthony; Tangen, Ingvild L; Tea, Muy-Kheng; Teixeira, Manuel R; Lubinski, Jan; Terry, Kathryn L; Terry, Mary Beth; Thomassen, Mads; Thompson, Pamela J; Glendon, Gord; Tihomirova, Laima; Blomqvist, Carl; Tischkowitz, Marc; Toland, Amanda Ewart; Tollenaar, Rob A E M; Lundvall, Lene; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tsimiklis, Helen; Tung, Nadine; Godwin, Andrew K; Tworoger, Shelley S; Tyrer, Jonathan P; Bogdanova, Natalia V; Vachon, Celine M; Lurie, Galina; Van 't Veer, Laura J (Academic Press Inc Elsevier Science, 2016-05)
    Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370.
  • Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

    Dunning, Alison M; Michailidou, Kyriaki; Kuchenbaecker, Karoline B; Thompson, Deborah; French, Juliet D; Beesley, Jonathan; Healey, Catherine S; Kar, Siddhartha; Pooley, Karen A; Lopez-Knowles, Elena; Dicks, Ed; Gronwald, Jacek; Huzarski, Tomasz; Barkardottir, Rosa B; Laframboise, Rachel; Soucy, Penny; Montagna, Marco; Agata, Simona; Teixeira, Manuel R; Park, Sue Kyung; Hills, Margaret; Cox, Angela; Lindor, Noralane; Couch, Fergus J; Tischkowitz, Marc; Foretova, Lenka; Vijai, Joseph; Offit, Kenneth; Singer, Christian F; Rappaport, Christine; Phelan, Catherine M; Greene, Mark H; Cross, Simon S; Jarosz, Monika; Mai, Phuong L; Rennert, Gad; Imyanitov, Evgeny N; Hulick, Peter J; Phillips, Kelly-Anne; Piedmonte, Marion; Mulligan, Anna Marie; Glendon, Gord; Bojesen, Anders; Blot, William; Thomassen, Mads; Drury, Suzie; Caligo, Maria A; Yoon, Sook-Yee; Friedman, Eitan; Laitman, Yael; Borg, Ake; von Wachenfeldt, Anna; Ehrencrona, Hans; Rantala, Johanna; Cai, Qiuyin; Olopade, Olufunmilayo I; Ganz, Patricia A; Canisius, Sander; Nussbaum, Robert L; Gayther, Simon A; Nathanson, Katherine L; Domchek, Susan M; Arun, Banu K; Mitchell, Gillian; Karlan, Beth Y; Ghoussaini, Maya; Lester, Jenny; Maskarinec, Gertraud; Woolcott, Christy; Bolla, Manjeet K; Scott, Christopher; Stone, Jennifer; Apicella, Carmel; Tamimi, Rulla; Luben, Robert; Khaw, Kay-Tee; Perkins, Barbara J; Helland, Åslaug; Haakensen, Vilde; Dowsett, Mitch; Pharoah, Paul D P; Dennis, Joe; Simard, Jacques; Hall, Per; García-Closas, Montserrat; Vachon, Celine; Chenevix-Trench, Georgia; Shah, Mitul; Antoniou, Antonis C; Easton, Douglas F; Edwards, Stacey L; Wang, Qin; Hopper, John L; Southey, Melissa C; Broeks, Annegien; Schmidt, Marjanka K; Lophatananon, Artitaya; Muir, Kenneth; Choi, Ji-Yeob; Beckmann, Matthias W; Fasching, Peter A; Dos-Santos-Silva, Isabel; Peto, Julian; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Kang, Daehee; Bojesen, Stig E; Flyger, Henrik; González-Neira, Anna; Perez, Jose I A; Anton-Culver, Hoda; Eunjung, Lee; Arndt, Volker; Brenner, Hermann; Meindl, Alfons; Schmutzler, Rita K; Lee, Soo Chin; Brauch, Hiltrud; Hamann, Ute; Aittomäki, Kristiina; Blomqvist, Carl; Ito, Hidemi; Matsuo, Keitaro; Bogdanova, Natasha; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Barrowdale, Daniel; Kosma, Veli-Matti; Mannermaa, Arto; Tseng, Chiu-Chen; Wu, Anna H; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Rudolph, Anja; Peterlongo, Paolo; Radice, Paolo; Hartman, Mikael; Olson, Janet E; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Henderson, Brian E; Goldberg, Mark S; Teo, Soo H; Yip, Cheng Har; Nord, Silje; Borresen-Dale, Anne-Lise; Kabisch, Maria; Kristensen, Vessela; Long, Jirong; Zheng, Wei; Pylkäs, Katri; Winqvist, Robert; Andrulis, Irene L; Knight, Julia A; Devilee, Peter; Seynaeve, Caroline; Figueroa, Jonine; Torres, Diana; Sherman, Mark E; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; van den Ouweland, Ans M W; Humphreys, Keith; Gao, Yu-Tang; Shu, Xiao-Ou; Jakubowska, Anna; Lubinski, Jan; Brennan, Paul; Sangrajrang, Suleeporn; Ambrosone, Christine B; Toland, Amanda E; Shen, Chen-Yang; Sinnott-Armstrong, Nicholas A; Wu, Pei-Ei; Orr, Nick; Swerdlow, Anthony; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Kapuscinski, Miroslav; John, Esther M; Terry, Mary Beth; Daly, Mary B; Sallari, Richard C; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ejlertsen, Bent; Hansen, Thomas V O; Hillman, Kristine M; Osorio, Ana; Benitez, Javier; Rando, Rachel; Weitzel, Jeffrey N; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Papi, Laura; Ottini, Laura; Konstantopoulou, Irene; Kaufmann, Susanne; Apostolou, Paraskevi; Garber, Judy; Rashid, Muhammad Usman; Frost, Debra; Izatt, Louise; Ellis, Steve; Godwin, Andrew K; Arnold, Norbert; Niederacher, Dieter; Rhiem, Kerstin; Sivakumaran, Haran; Bogdanova-Markov, Nadja; Sagne, Charlotte; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Sinilnikova, Olga M; Mazoyer, Sylvie; Isaacs, Claudine; Claes, Kathleen B M; De Leeneer, Kim; de la Hoya, Miguel; Moradi Marjaneh, Mahdi; Caldes, Trinidad; Nevanlinna, Heli; Khan, Sofia; Mensenkamp, Arjen R; Hooning, Maartje J; Rookus, Matti A; Kwong, Ava; Olah, Edith; Diez, Orland; Brunet, Joan; Lee, Jason S; Pujana, Miquel Angel; [ 1 ] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England [ 2 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England [ 3 ] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld, Australia [ 4 ] Breakthrough Breast Canc Res Ctr, Breast Canc Res, London, England [ 5 ] Royal Marsden Hosp, Acad Biochem, London SW3 6JJ, England [ 6 ] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA [ 7 ] MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA [ 8 ] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands [ 9 ] Univ Melbourne, Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia [ 10 ] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia [ 11 ] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England [ 12 ] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England [ 13 ] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Comprehens Canc Ctr Erlangen Nuremberg Metropolit, D-91054 Erlangen, Germany [ 14 ] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA [ 15 ] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England [ 16 ] Kings Coll London, Guys Hosp, Div Canc Studies, Res Oncol, London, England [ 17 ] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England [ 18 ] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England [ 19 ] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany [ 20 ] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany [ 21 ] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany [ 22 ] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany [ 23 ] INSERM, Ctr Res Epidemiol & Populat Hlth, Environm Epidemiol Canc, Villejuif, France [ 24 ] Univ Paris Sud, Villejuif, France [ 25 ] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Herlev, Denmark [ 26 ] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark [ 27 ] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark [ 28 ] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Herlev, Denmark [ 29 ] Spanish Natl Canc Ctr CNIO, Human Canc Genet Program, Madrid, Spain [ 30 ] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain [ 31 ] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA [ 32 ] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA [ 33 ] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany [ 34 ] German Canc Res Ctr, German Canc Consortium, Heidelberg, Germany [ 35 ] Tech Univ Munich, Dept Obstet & Gynaecol, D-80290 Munich, Germany [ 36 ] Univ Hosp Cologne, Dept Obstet & Gynaecol, Div Mol Gynecooncol, Cologne, Germany [ 37 ] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Cologne, Germany [ 38 ] Univ Hosp, Ctr Integrated Oncol, Cologne, Germany [ 39 ] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Auerbachstr 112, Stuttgart, Germany [ 40 ] Univ Tubingen, Tubingen, Germany [ 41 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany [ 42 ] Helsinki Univ Cent Hosp, Dept Clin Genet, Helsinki, Finland [ 43 ] Univ Helsinki, Helsinki Univ Cent Hosp, Dept Oncol, Helsinki, Finland [ 44 ] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Aichi, Japan [ 45 ] Aichi Canc Ctr Res Inst, Div Mol Med, Nagoya, Aichi, Japan [ 46 ] Hannover Med Sch, Radiat Oncol Res Unit, Hannover, Germany [ 47 ] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany [ 48 ] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden [ 49 ] Karolinska Univ Hosp, Dept Oncol Pathol, Stockholm, Sweden [ 50 ] Kuopio Univ Hosp, Ctr Canc, SF-70210 Kuopio, Finland [ 51 ] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Kuopio, Finland [ 52 ] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, SF-70210 Kuopio, Finland [ 53 ] Vesalius Res Ctr, Leuven, Belgium [ 54 ] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium [ 55 ] Univ Hosp Leuven, Dept Gen Med Oncol, Multidisciplinary Breast Ctr, Leuven, Belgium [ 56 ] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany [ 57 ] Univ Med Ctr Hamburg Eppendorf, UCCH, Hamburg, Germany [ 58 ] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy [ 59 ] Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Mol Basis Genet Risk & Genet Testing, Milan, Italy [ 60 ] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA [ 61 ] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia [ 62 ] McGill Univ, Dept Med, Montreal, PQ, Canada [ 63 ] McGill Univ, Royal Victoria Hosp, Div Clin Epidemiol, Montreal, PQ H3A 1A1, Canada [ 64 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia [ 65 ] Univ Malaya, Med Ctr, Canc Res Inst, Breast Canc Res Unit, Kuala Lumpur, Malaysia [ 66 ] Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Genet, Oslo, Norway [ 67 ] Univ Oslo, Inst Clin Med, Oslo, Norway [ 68 ] Univ Oslo, Oslo Univ Hosp, Dept Clin Mol Biol, Oslo, Norway [ 69 ] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, Nashville, TN 37212 USA [ 70 ] Univ Oulu, NordLab Oulu Univ Hosp, Dept Clin Chem, Lab Canc Genet & Tumor Biol, Oulu, Finland [ 71 ] Univ Oulu, NordLab Oulu Univ Hosp, Bioctr Oulu, Oulu, Finland [ 72 ] Northern Finland Lab Ctr NordLab, Lab Canc Genet & Tumor Biol, Oulu, Finland [ 73 ] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada [ 74 ] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada [ 75 ] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada [ 76 ] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada [ 77 ] Leiden Univ Med Ctr, Dept Pathol, Leiden, Netherlands [ 78 ] Leiden Univ Med Ctr, Dept Human Genet, Leiden, Netherlands [ 79 ] Erasmus MC, Dept Med Oncol, Rotterdam, Netherlands [ 80 ] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA [ 81 ] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden [ 82 ] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands [ 83 ] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China [ 84 ] Univ Sheffield, Sheffield Canc Res, Dept Oncol, Sheffield, S Yorkshire, England [ 85 ] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England [ 86 ] Int Epidemiol Inst, Rockville, MD USA [ 87 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea [ 88 ] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea [ 89 ] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea [ 90 ] Natl Univ Hlth Syst, Dept Haematol Oncol, Singapore, Singapore [ 91 ] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore [ 92 ] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore [ 93 ] Natl Univ Hlth Syst, Dept Surg, Singapore, Singapore [ 94 ] Pontificia Univ Javerianar, Inst Human Genet, Bogota, Colombia [ 95 ] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland [ 96 ] Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France [ 97 ] Natl Canc Inst, Bangkok, Thailand [ 98 ] Roswell Pk Canc Inst, Buffalo, NY 14263 USA [ 99 ] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA [ 100 ] China Med Univ, Sch Publ Hlth, Taichung, Taiwan [ 101 ] Acad Sinica, Inst Biomed Sci, Taiwan Biobank, Taipei, Taiwan [ 102 ] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Div Canc Studies, London SW3 6JB, England [ 103 ] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England [ 104 ] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England [ 105 ] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia [ 106 ] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA [ 107 ] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA [ 108 ] Fox Chase Canc Ctr, Dept Clin Genet, 7701 Burholme Ave, Philadelphia, PA 19111 USA [ 109 ] Univ Utah, Sch Med, Dept Dermatol, Huntsman Canc Inst, Salt Lake City, UT USA [ 110 ] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT USA [ 111 ] State Res Inst Ctr Innovat Med, Vilnius, Lithuania [ 112 ] Latvian Biomed Res & Study Ctr, Riga, Latvia [ 113 ] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA [ 114 ] Univ Pretoria, Dept Genet, ZA-0002 Pretoria, South Africa [ 115 ] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA [ 116 ] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark [ 117 ] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark [ 118 ] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain [ 119 ] Biomed Network Rare Dis CIBERER, Madrid, Spain [ 120 ] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genotyping CEGEN Unit, Madrid, Spain [ 121 ] City Hope Clin Canc Genom Community Res Network, Duarte, CA USA [ 122 ] City Hope Natl Med Ctr, Clin Canc Genet, Duarte, CA USA [ 123 ] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy [ 124 ] Ist Nazl Tumori, Fdn Ist Ricovero & Cura Carattere Sci, Dept Prevent & Predict Med, Unit Med Genet, Via Venezian 1, I-20133 Milan, Italy [ 125 ] Univ Florence, Dept Biomed Expt & Clin Sci, Unit Med Genet, Florence, Italy [ 126 ] Univ Roma La Sapienza, Dept Mol Med, Piazzale Aldo Moro 5, I-00185 Rome, Italy [ 127 ] Aghia Paraskevi Attikis, Natl Ctr Sci Res Demokritos, INRASTES Inst Nucl & Radiol Sci & Technol, Mol Diagnost Lab, Athens, Greece [ 128 ] Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02115 USA [ 129 ] Shaukat Khanum Mem Canc Hosp & Res Ctr, Dept Basic Sci, Lahore, Pakistan [ 130 ] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Clin Genet, London, England [ 131 ] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA [ 132 ] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Gynaecol & Obstet, Campus Kiel, Kiel, Germany [ 133 ] Univ Dusseldorf, Dusseldorf, Germany [ 134 ] Univ Hosp Cologne, Ctr Mol Med Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, Cologne, Germany [ 135 ] Univ Hosp Cologne, Ctr Mol Med Cologne, Ctr Integrated Oncol, Cologne, Germany [ 136 ] Univ Munster, Inst Human Genet, D-48149 Munster, Germany [ 137 ] Univ Lyon 1, CNRS UMR 5286, INSERM U1052, Ctr Rech Cancerol Lyon, F-69365 Lyon, France [ 138 ] Inst Curie, Dept Tumour Biol, Paris, France [ 139 ] Univ Paris 05, Sorbonne Paris Cite, Paris, France [ 140 ] Hosp Civils Lyon, Ctr Leon Berard, Unite Mixte Genet Constitutionnelle Canc Frequent, Lyon, France [ 141 ] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA [ 142 ] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium [ 143 ] Hosp Clin San Carlos, IdISSC, Mol Oncol Lab, Madrid, Spain [ 144 ] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland [ 145 ] Univ Helsinki, Cent Hosp, Helsinki, Finland [ 146 ] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands [ 147 ] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands [ 148 ] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands [ 149 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China [ 150 ] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China [ 151 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary [ 152 ] Vall dHebron Univ Hosp, VHIO, Oncogenet Lab, Barcelona, Spain [ 153 ] Catalan Inst Oncol, IDIBGI, Hereditary Canc Program, Genet Counseling Unit, Girona, Spain [ 154 ] Catalan Inst Oncol, IDIBELL Bellvitge Biomed Res Inst, Breast Canc & Syst Biol Unit, Barcelona, Spain [ 155 ] Univ Iceland, Fac Med, Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital     University of Iceland [ 156 ] Univ Iceland, Fac Med, Biomed Ctr BMC, Reykjavik, Iceland [ 157 ] Ctr Hosp Univ Quebec, Div Med Genet, Quebec City, PQ, Canada [ 158 ] Univ Laval, Quebec City, PQ, Canada [ 159 ] Ctr Hosp Univ Quebec, Quebec City, PQ, Canada [ 160 ] IRCCS, IOV, Immunol & Mol Oncol Unit, Padua, Italy [ 161 ] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal [ 162 ] Univ Porto, Biomed Sci Inst ICBAS, Rua Campo Alegre 823, P-4100 Oporto, Portugal [ 163 ] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA [ 164 ] McGill Univ, Program Canc Genet, Montreal, PQ, Canada [ 165 ] Masaryk Univ, Masaryk Mem Canc Inst, Brno, Czech Republic [ 166 ] Masaryk Univ, Fac Med, Brno, Czech Republic [ 167 ] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA [ 168 ] Med Univ Vienna, Ctr Comprehens Canc, Dept Obstet & Gynecol, Vienna, Austria [ 169 ] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Tampa, FL 33682 USA [ 170 ] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, US NIH, Rockville, MD USA [ 171 ] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel [ 172 ] Technion Israel Inst Technol, Bruce Rappaport Fac Med, POB 9649, IL-31096 Haifa, Israel [ 173 ] Clalit Natl Israeli Canc Control Ctr, Haifa, Israel [ 174 ] NN Petrov Oncol Res Inst, St Petersburg, Russia [ 175 ] NorthShore Univ Hlth Syst, Ctr Med Genet, Evanston, IL USA [ 176 ] Peter MacCallum Canc Ctr, Div Canc Med, East Melbourne, Vic, Australia [ 177 ] Roswell Pk Canc Inst, Stat & Data Management Ctr, NRG Oncol, Buffalo, NY 14263 USA [ 178 ] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada [ 179 ] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada [ 180 ] Vejle Hosp, Dept Clin Genet, Vejle, Denmark [ 181 ] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark [ 182 ] Univ Pisa, Dept Lab Med, Sect Genet Oncol, Pisa, Italy [ 183 ] Univ Hosp Pisa, Pisa, Italy [ 184 ] Univ Malaya, Univ Malaya Med Ctr, Fac Med, Univ Malaya Canc Res Inst, Kuala Lumpur, Malaysia [ 185 ] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel [ 186 ] Lund Univ, Dept Oncol, Lund, Sweden [ 187 ] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden [ 188 ] Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden [ 189 ] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden [ 190 ] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 191 ] Univ Calif Los Angeles, Sch Med, Johnsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA [ 192 ] Univ Calif Los Angeles, Sch Publ Hlth, Johnsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA [ 193 ] Univ Calif San Francisco, Dept Med & Genet, San Francisco, CA 94143 USA [ 194 ] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA [ 195 ] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA [ 196 ] Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic, Australia [ 197 ] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia [ 198 ] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA [ 199 ] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA [ 200 ] Dalhousie Univ, Dept Obstet Gynaecol & Pediat, Halifax, NS, Canada [ 201 ] Univ Western Australia, Ctr Genet Origins Hlth & Dis, Perth, WA 6009, Australia [ 202 ] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA [ 203 ] Harvard Univ, Sch Med, Boston, MA USA [ 204 ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA [ 205 ] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, 665 Huntington Ave, Boston, MA 02115 USA [ 206 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Clin Gerontol, Cambridge, England (Nature Publishing Group, 2016-04)
    We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.
  • Translational research—the need of a new bioethics approach

    Hostiuc, Sorin; Moldoveanu, Alin; Dascălu, Maria-Iuliana; Unnthorsson, Runar; Jóhannesson, Ómar I.; Marcus, Ioan; [ 1 ] Carol Davila Univ, Dept Legal Med & Bioeth, Bucharest, Romania [ 2 ] Natl Inst Legal Med, Bucharest, Romania [ 3 ] Univ Politehn Bucuresti, Fac Automat Control & Comp, Bucharest, Romania [ 4 ] Univ Politehn Bucuresti, Dept Engn Foreign Languages, Bucharest, Romania [ 5 ] Univ Iceland, Fac Ind Engn Mech Engn & Comp Sci, Reykjavik, Iceland [ 6 ] Univ Iceland, Dept Psychol, Reykjavik, Iceland [ 7 ] Univ Agr Sci & Vet Med, Fac Vet Med, Dept Pathophysiol, Cluj Napoca, Romania (BioMed Central Ltd, 2016-01-15)
    Translational research tries to apply findings from basic science to enhance human health and well-being. Many phases of the translational research may include non-medical tasks (information technology, engineering, nanotechnology, biochemistry, animal research, economy, sociology, psychology, politics, and so on). Using common bioethics principles to these areas might sometimes be not feasible, or even impossible. However, the whole process must respect some fundamental, moral principles. The purpose of this paper is to argument the need for a different approach to the morality in translational bioethics, and to suggest some directions that might be followed when constructing such a bioethics. We will show that a new approach is needed and present a few ethical issues that are specific to the translational research.
  • Variations in Multiple Birth Rates and Impact on Perinatal Outcomes in Europe.

    Heino, Anna; Gissler, Mika; Hindori-Mohangoo, Ashna D; Blondel, Béatrice; Klungsøyr, Kari; Verdenik, Ivan; Mierzejewska, Ewa; Velebil, Petr; Sól Ólafsdóttir, Helga; Macfarlane, Alison; Zeitlin, Jennifer; [ 1 ] THL Natl Inst Hlth & Welf, Helsinki, Finland [ 2 ] TNO, Netherlands Org Appl Sci Res, Dept Child Hlth, Leiden, Netherlands [ 3 ] Anton de Kom Univ Suriname, Fac Med Sci, Dept Publ Hlth, Paramaribo, Surinam [ 4 ] Paris Descartes Univ, Ctr Epidemiol & Biostat U1153, Obstetr Perinatal & Paediat Epidemiol Res Team, INSERM, Paris, France [ 5 ] Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5018 Bergen, Norway [ 6 ] Norwegian Inst Publ Hlth, Med Birth Registry Norway, N-5018 Bergen, Norway [ 7 ] Univ Ljubljana, Med Ctr, Ljubljana 61000, Slovenia [ 8 ] Natl Res Inst Mother & Child, Dept Epidemiol, Warsaw, Poland [ 9 ] Inst Care Mother & Child, Prague, Czech Republic [ 10 ] Landspitali Univ Hosp, Dept Obstet & Gynaecol, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital (Public Library Science, 2016)
    Infants from multiple pregnancies have higher rates of preterm birth, stillbirth and neonatal death and differences in multiple birth rates (MBR) exist between countries. We aimed to describe differences in MBR in Europe and to investigate the impact of these differences on adverse perinatal outcomes at a population level.
  • Wide differences in mode of delivery within Europe: risk-stratified analyses of aggregated routine data from the Euro-Peristat study.

    Macfarlane, A J; Blondel, B; Mohangoo, A D; Cuttini, M; Nijhuis, J; Novak, Z; Ólafsdóttir, H S; Zeitlin, J; [ 1 ] City Univ London, Ctr Maternal & Child Hlth Res, London EC1V 0HB, England [ 2 ] Paris Descartes Univ, INSERM, Obstet Perinatal & Paediat Epidemiol Res Team, Ctr Epidemiol & Biostat U1153, Paris, France [ 3 ] TNO, Netherlands Org Appl Sci Res, Dept Child Hlth, Leiden, Netherlands [ 4 ] Bambino Gesu Pediat Hosp, Res Unit Perinatal Epidemiol, Rome, Italy [ 5 ] Maastricht Univ, Med Ctr, GROW Sch Oncol & Dev Biol, Dept Obstet & Gynaecol, Maastricht, Netherlands [ 6 ] Llubjana Univ, Univ Med Ctr, Perinatol Unit, Llubjana, Slovenia [ 7 ] Landspitali Univ Hosp, Dept Obstet & Gynaecol, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital (Wiley-Blackwell, 2016-03)
    To use data from routine sources to compare rates of obstetric intervention in Europe both overall and for subgroups at higher risk of intervention.
  • HLA class II sequence variants influence tuberculosis risk in populations of European ancestry

    Sveinbjornsson, Gardar; Gudbjartsson, Daniel F; Halldorsson, Bjarni V; Kristinsson, Karl G; Gottfredsson, Magnus; Barrett, Jeffrey C; Gudmundsson, Larus J; Blondal, Kai; Gylfason, Arnaldur; Gudjonsson, Sigurjon Axel; Helgadottir, Hafdis T; Jonasdottir, Adalbjorg; Jonasdottir, Aslaug; Karason, Ari; Kardum, Ljiljana Bulat; Knežević, Jelena; Kristjansson, Helgi; Kristjansson, Mar; Love, Arthur; Luo, Yang; Magnusson, Olafur T; Sulem, Patrick; Kong, Augustine; Masson, Gisli; Thorsteinsdottir, Unnur; Dembic, Zlatko; Nejentsev, Sergey; Blondal, Thorsteinn; Jonsdottir, Ingileif; Stefansson, Kari; [ 1 ] Amgen Inc, deCODE Genet, Reykjavik, Iceland [ 2 ] Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland [ 3 ] Reykjavik Univ, Sch Sci & Engn, Reykjavik, Iceland [ 4 ] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland [ 5 ] Natl Univ Hosp Iceland, Dept Clin Microbiol, Landspitali, Reykjavik, Iceland [ 6 ] Natl Univ Hosp Iceland, Dept Infect Dis, Landspitali, Reykjavik, Iceland [ 7 ] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England [ 8 ] Primary Hlth Care Capital Area, Div Communicable Dis Prevent & Control, Reykjavik, Iceland [ 9 ] Univ Rijeka, Dept Pulmonol, Clin Internal Med, Clin Hosp Ctr, Rijeka, Croatia [ 10 ] Univ Oslo, Fac Dent, Dept Oral Biol, Mol Genet Lab, Oslo, Norway [ 11 ] Rudjer Boskovic Inst, Div Mol Med, Zagreb, Croatia [ 12 ] Natl Univ Hosp Iceland, Landspitali, Dept Virol, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 13 ] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England [ 14 ] Natl Univ Hosp Iceland, Landspitali, Dept Immunol, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital (Nature Publishing Group, 2016-02-01)
    Mycobacterium tuberculosis infections cause 9 million new tuberculosis cases and 1.5 million deaths annually. To identify variants conferring risk of tuberculosis, we tested 28.3 million variants identified through whole-genome sequencing of 2,636 Icelanders for association with tuberculosis (8,162 cases and 277,643 controls), pulmonary tuberculosis (PTB) and M. tuberculosis infection. We found association of three variants in the region harboring genes encoding the class II human leukocyte antigens (HLAs): rs557011[T] (minor allele frequency (MAF) = 40.2%), associated with M. tuberculosis infection (odds ratio (OR) = 1.14, P = 3.1 × 10(-13)) and PTB (OR = 1.25, P = 5.8 × 10(-12)), and rs9271378[G] (MAF = 32.5%), associated with PTB (OR = 0.78, P = 2.5 × 10(-12))-both located between HLA-DQA1 and HLA-DRB1-and a missense variant encoding p.Ala210Thr in HLA-DQA1 (MAF = 19.1%, rs9272785), associated with M. tuberculosis infection (P = 9.3 × 10(-9), OR = 1.14). We replicated association of these variants with PTB in samples of European ancestry from Russia and Croatia (P < 5.9 × 10(-4)). These findings show that the HLA class II region contributes to genetic risk of tuberculosis, possibly through reduced presentation of protective M. tuberculosis antigens to T cells.
  • GWAS for executive function and processing speed suggests involvement of the CADM2 gene.

    Ibrahim-Verbaas, C A; Bressler, J; Debette, S; Schuur, M; Smith, A V; Bis, J C; Davies, G; Trompet, S; Smith, J A; Wolf, C; Chibnik, L B; Yu, L; DeStefano, A L; Beiser, A; Garcia, M; Rotter, J I; Nöthen, M M; Hofman, A; Slagboom, P E; Westendorp, R G J; Buckley, B M; Wright, A F; Räikkönen, K; Wolf, P A; Uitterlinden, A G; Psaty, B M; Grabe, H J; Bandinelli, S; Chasman, D I; Lambert, J-C; Porteous, D J; Price, J F; Wilson, J F; Sachdev, P S; Ferrucci, L; Attia, J R; Rudan, I; Hayward, C; Liu, Y; Cichon, S; Franke, L; Schmidt, H; Ding, J; de Craen, A J M; Fornage, M; Bennett, D A; Deary, I J; Schmidt, C O; Vitart, V; Ikram, M A; Launer, L J; Fitzpatrick, A L; Seshadri, S; van Duijn, C M; Mosley, T H; Kirin, M; Petrovic, K; Polasek, O; Mather, K A; Zgaga, L; Fawns-Ritchie, C; Hoffmann, P; Karjalainen, J; Lahti, J; Llewellyn, D J; Chouraki, V; Sun, Q; Resnick, S M; Rose, L M; Oldmeadow, C; Stewart, M; Smith, B H; Gudnason, V; Au, R; Yang, Q; Mirza, S S; Jukema, J W; deJager, P L; Harris, T B; Liewald, D C; Amin, N; Coker, L H; Stegle, O; Lopez, O L; Fehrmann, R S N; Schmidt, R; Teumer, A; Ford, I; Karbalai, N; Becker, J T; Jonsdottir, M K; Herms, S; Nalls, M; Zhao, W; Turner, S T; Yaffe, K; Lohman, K; van Swieten, J C; Kardia, S L R; Pilling, L C; Knopman, D S; Meeks, W M; Heiss, G; Holliday, E G; Schofield, P W; Tanaka, T; Stott, D J; Wang, J; Ridker, P; Gow, A J; Eiriksdottir, G; Pattie, A; Starr, J M; Hocking, L J; Armstrong, N J; McLachlan, S; Shulman, J M; Scott, R J; Kochan, N A; Palotie, A; Hsieh, Y-C; Eriksson, J G; Penman, A; Gottesman, R F; Oostra, B A; Grodstein, F; [ 1 ] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands [ 2 ] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands [ 3 ] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA [ 4 ] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA [ 5 ] Univ Bordeaux, Epidemiol & Biostat, U897, INSERM, Bordeaux, France [ 6 ] Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France [ 7 ] Iceland Heart Assoc, Kopavogur, Iceland [ 8 ] Univ Iceland, Fac Med, Reykjavik, Iceland [ 9 ] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA [ 10 ] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland [ 11 ] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands [ 12 ] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands [ 13 ] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA [ 14 ] Max Planck Inst Psychiat, RG Stat Genet, Munich, Germany [ 15 ] Brigham & Womens Hosp, Div Neurol, Program Translat Neuropsychiat Gen, Boston, MA 02115 USA [ 16 ] Wake Forest Sch Med, Dept Epidemiol, Winston Salem, NC USA [ 17 ] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland [ 18 ] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland [ 19 ] Med Univ & Gen Hosp Graz, Dept Neurol, Graz, Austria [ 20 ] Univ Split, Dept Publ Hlth, Split, Croatia [ 21 ] Trintiy Coll Dublin, Dept Publ Hlth & Primary Care, Dublin, Ireland [ 22 ] Res Ctr Juelich, Inst Neurosci & Med INM1, Julich, Germany [ 23 ] Univ Basel, Dept Biomed, Div Med Genet, Basel, Switzerland [ 24 ] Univ Bonn, Inst Human Genet, Life & Brain Res Ctr, Dept Genom, Bonn, Germany [ 25 ] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands [ 26 ] Univ Helsinki, Inst Behav Sci, Helsinki, Finland [ 27 ] Folkhalsan Res Ctr, Helsinki, Finland [ 28 ] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter, Devon, England [ 29 ] Univ Med Greifswald, Inst Community Med, Greifswald, Germany [ 30 ] Univ New S Wales, UNSW Med, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia [ 31 ] Univ Lille Nord France, Inst Pasteur Lille, U1167, INSERM, Lille, France [ 32 ] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA [ 33 ] Harvard Univ, Sch Med, Boston, MA USA [ 34 ] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA [ 35 ] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA [ 36 ] Univ Newcastle, Hunter Med Res Inst, Newcastle, NSW 2300, Australia [ 37 ] Univ Newcastle, Fac Hlth, Newcastle, NSW 2300, Australia [ 38 ] Univ Dundee, Med Res Inst, Dundee, Scotland [ 39 ] NHLBI, Framingham Heart Study, Framingham, MA USA [ 40 ] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA [ 41 ] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands [ 42 ] Netherlands Consortium Hlth Ageing, Leiden, Netherlands [ 43 ] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA [ 44 ] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland [ 45 ] Wake Forest Sch Med, Div Publ Hlth Sci & Neurol, Winston Salem, NC USA [ 46 ] Max Planck Inst Intelligent Syst, Max Planck Inst Dev Biol, Tubingen, Germany [ 47 ] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA [ 48 ] Univ Med Greifswald, Interfaculty Inst Genet & Funct Genom, Greifswald, Germany [ 49 ] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland [ 50 ] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA [ 51 ] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA [ 52 ] Landspitali Hosp, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 53 ] NIA, Lab Neurogenet, Bethesda, MD 20892 USA [ 54 ] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN USA [ 55 ] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA [ 56 ] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA [ 57 ] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA USA [ 58 ] San Francisco VA Med Ctr, San Francisco, CA USA [ 59 ] Mayo Clin, Dept Neurol, Rochester, MN USA [ 60 ] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA [ 61 ] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA [ 62 ] Univ Newcastle, Fac Hlth, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia [ 63 ] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA [ 64 ] Univ Glasgow, Dept Cardiovasc & Med Sci, Glasgow, Lanark, Scotland [ 65 ] Alzheimer Scotland Res Ctr, Edinburgh, Midlothian, Scotland [ 66 ] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland [ 67 ] Garvan Inst Med Res, Canc Res Program, Sydney, NSW, Australia [ 68 ] Univ New S Wales, Sch Math & Stat, Sydney, NSW, Australia [ 69 ] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW, Australia [ 70 ] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA [ 71 ] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Dept Mol & Human Genet, Houston, TX 77030 USA [ 72 ] Univ Exeter, Sch Med, Epidemiol & Publ Hlth Grp, Exeter, Devon, England [ 73 ] Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW, Australia [ 74 ] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England [ 75 ] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland [ 76 ] Univ Helsinki, Dept Med Genet, Helsinki, Finland [ 77 ] Univ Cent Hosp, Helsinki, Finland [ 78 ] Taipei Med Univ, Sch Publ Hlth, Taipei, Taiwan [ 79 ] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland [ 80 ] Natl Inst Hlth & Welf, Helsinki, Finland [ 81 ] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland [ 82 ] Vasa Cent Hosp, Vaasa, Finland [ 83 ] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA [ 84 ] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA [ 85 ] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA [ 86 ] Cedars Sinai Med Ctr, Med Genet Inst, Los Angeles, CA 90048 USA [ 87 ] Harbor UCLA Med Ctr, Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA [ 88 ] Harbor UCLA Med Ctr, Dept Pediat, Div Genet Outcomes, Torrance, CA 90509 USA [ 89 ] German Ctr Neurodegenerat Dis DZNE, Bonn, Germany [ 90 ] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands [ 91 ] Leiden Acad Vital & Ageing, Leiden, Netherlands [ 92 ] Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland [ 93 ] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands [ 94 ] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA [ 95 ] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA [ 96 ] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA [ 97 ] HELIOS Hosp Stralsund, Univ Med Greifswald, Dept Psychiat & Psychotherapy, Stralsund, Germany [ 98 ] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy [ 99 ] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland [ 100 ] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA [ 101 ] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA [ 102 ] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA [ 103 ] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands [ 104 ] Univ Mississippi, Med Ctr, Dept Med & Neurol, Jackson, MS 39216 USA (Nature Publishing Group, 2016-02)
    To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.
  • Ensuring Effective Prevention of Iodine Deficiency Disorders.

    Völzke, Henry; Caron, Philippe; Dahl, Lisbeth; de Castro, João J; Erlund, Iris; Gaberšček, Simona; Gunnarsdottir, Ingibjörg; Hubalewska-Dydejczyk, Alicja; Ittermann, Till; Ivanova, Ludmila; Karanfilski, Borislav; Khattak, Rehman M; Kusić, Zvonko; Laurberg, Peter; Lazarus, John H; Markou, Kostas B; Moreno-Reyes, Rodrigo; Nagy, Endre V; Peeters, Robin P; Pīrāgs, Valdis; Podoba, Ján; Rayman, Margaret P; Rochau, Ursula; Siebert, Uwe; Smyth, Peter P; Thuesen, Betina H; Troen, Aron; Vila, Lluís; Vitti, Paolo; Zamrazil, Vaclav; Zimmermann, Michael B; [ 1 ] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany [ 2 ] Ctr Hosp Univ Larrey, Dept Endocrinol, Toulouse, France [ 3 ] Natl Inst Nutr & Seafood Res, Human Studies, Bergen, Norway [ 4 ] Hosp Forcas Armadas, Dept Endocrinol, Lisbon, Portugal [ 5 ] Natl Inst Hlth & Welf, Dis Risk Unit, Helsinki, Finland [ 6 ] Univ Med Ctr, Dept Nucl Med, Ljubljana, Slovenia [ 7 ] Univ Iceland, Unit Nutr Res, Reykjavik, Iceland [ 8 ] Landspitali Natl Univ Hosp, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 9 ] Jagiellonian Univ, Coll Med, Dept Endocrinol, Krakow, Poland [ 10 ] Sofia Univ Sv Kliment Ohridski, Fac Med, Sofia, Bulgaria [ 11 ] Ctr Reg Policy Res & Cooperat Studiorum, Skopje, Macedonia [ 12 ] Univ Zagreb, Sch Med, Univ Hosp Ctr Sestre Milosrdnice, Dept Oncol & Nucl Med, Zagreb 41001, Croatia [ 13 ] Aalborg Univ Hosp, Dept Endocrinol, Aalborg, Denmark [ 14 ] Aalborg Univ Hosp, Dept Clin Med, Aalborg, Denmark [ 15 ] Aalborg Univ, Aalborg, Denmark [ 16 ] Cardiff Univ, Inst Mol Med, Cardiff CF10 3AX, S Glam, Wales [ 17 ] Inst Univ Patras Med Sch, Dept Endocrinol, Patras, Greece [ 18 ] Univ Libre Bruxelles, Erasme Hosp, Dept Nucl Med, Brussels, Belgium [ 19 ] Univ Debrecen, Div Endocrinol, Debrecen, Hungary [ 20 ] Erasmus MC, Rotterdam Thyroid Ctr, Dept Internal Med, Rotterdam, Netherlands [ 21 ] Univ Latvia, Dept Internal Med, Riga, Latvia [ 22 ] Slovakian Med Univ, Dept Endocrinol, Bratislava, Slovakia [ 23 ] Univ Surrey, Fac Hlth & Med Sci, Dept Nutr Sci, Guildford GU2 5XH, Surrey, England [ 24 ] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth, Hlth Serv Res & Hlth Technol Assessment, Hall In Tirol, Austria [ 25 ] Natl Univ Ireland, Galway, Ireland [ 26 ] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland [ 27 ] Rigshosp, Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark [ 28 ] Hebrew Univ Jerusalem, Inst Biochem Food Sci & Nutr, Jerusalem, Israel [ 29 ] Hosp St Joan Despi Moises, Dept Endocrinol & Nutr, Barcelona, Spain [ 30 ] Univ Pisa, Dept Clin & Expt Med, Pisa, Italy [ 31 ] Inst Endocrinol, Prague, Czech Republic [ 32 ] Zurich Dept Hlth Sci & Technol, Swiss Fed Inst Technol, Zurich, Switzerland (Mary Ann Liebert, 2016-02)
    Programs initiated to prevent iodine deficiency disorders (IDD) may not remain effective due to changes in government policies, commercial factors, and human behavior that may affect the efficacy of IDD prevention programs in unpredictable directions. Monitoring and outcome studies are needed to optimize the effectiveness of IDD prevention.
  • Socioeconomic inequalities in stillbirth rates in Europe: measuring the gap using routine data from the Euro-Peristat Project.

    Zeitlin, Jennifer; Mortensen, Laust; Prunet, Caroline; Macfarlane, Alison; Hindori-Mohangoo, Ashna D; Gissler, Mika; Szamotulska, Katarzyna; van der Pal, Karin; Bolumar, Francisco; Andersen, Anne-Marie Nybo; Ólafsdóttir, Helga Sól; Zhang, Wei-Hong; Blondel, Béatrice; Alexander, Sophie; [ 1 ] Paris Descartes Univ, Obstet Perinatal & Pediat Epidemiol Res Team Epop, Sorbonne Paris Cite,DHU Risks Pregnancy, Inserm,UMR 1153,Ctr Epidemiol & Stat, 53 Ave Observ, F-75014 Paris, France [ 2 ] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark [ 3 ] City Univ London, Ctr Maternal & Child Hlth Res, London EC1V 0HB, England [ 4 ] Netherlands Org Appl Sci Res, Dept Child Hlth, TNO, Leiden, Netherlands [ 5 ] THL Natl Inst Hlth & Welf, Helsinki, Finland [ 6 ] Natl Res Inst Mother & Child, Dept Epidemiol, Kasprzaka 17 A, PL-01211 Warsaw, Poland [ 7 ] Univ Alcala De Henares, Dept Publ Hlth Sci, Madrid, Spain [ 8 ] Landspitali V Hringbraut, Landspitali Univ Hosp, Dept Obstet & Gynaecol, Reykjavik, Iceland   Organization-Enhanced Name(s)      Landspitali National University Hospital [ 9 ] Univ Libre Bruxelles, Perinatal Epidemiol & Reprod Hlth Unit, Epidemiol Biostat & Clin Res Ctr, Sch Publ Hlth, Brussels, Belgium (BioMed Central Ltd, 2016)
    Previous studies have shown that socioeconomic position is inversely associated with stillbirth risk, but the impact on national rates in Europe is not known. We aimed to assess the magnitude of social inequalities in stillbirth rates in European countries using indicators generated from routine monitoring systems.
  • Inpatient drug utilization in Europe: nationwide data sources and a review of publications on a selected group of medicines (PROTECT project).

    Sabaté, Mònica; Ferrer, Pili; Ballarín, Elena; Rottenkolber, Marietta; Amelio, Justyne; Schmiedl, Sven; Reynolds, Robert; Klungel, Olaf; Ibáñez, Luisa; Addresses: [ 1 ] Fundacio Inst Catala Farmacol, Barcelona, Spain [ 2 ] Univ Hosp Vall dHebron, Dept Clin Pharmacol, Barcelona, Spain [Show the Organization-Enhanced name(s)] [ 3 ] Autonomous Univ Barcelona, Hosp Univ Vall dHebron, Dept Pharmacol Toxicol & Clin Therapeut, Barcelona 08029, Spain [Show the Organization-Enhanced name(s)] [ 4 ] Univ Munich, Inst Med Informat Sci Biometry & Epidemiol, Munich, Germany [ 5 ] Amgen Inc, Uxbridge, Middx, England [ 6 ] Helios Klin Wuppertal, Philipp Klee Inst Clin Pharmacol, Wuppertal, Germany [Show the Organization-Enhanced name(s)] [ 7 ] Univ Witten Herdecke, Fac Hlth, Sch Med, Dept Clin Pharmacol, Witten, Germany [Show the Organization-Enhanced name(s)] [ 8 ] Pfizer Res & Dev, Epidemiol, New York, NY USA [Show the Organization-Enhanced name(s)] [ 9 ] Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands (Wiley-Blackwell, 2015-03)
    Drug utilization (DU) studies in inpatient settings at a national level are rarely conducted. The main objective of this study was to review the general information on hospital medicine management in Europe and to report on the availability and characteristics of nationwide administrative drug consumption databases. A secondary objective was to perform a review of published studies on hospital DU of a group of selected drugs, focusing on methodological characteristics (ATC/DDD). General information on hospital drug management was retrieved from several websites, nationwide administrative drug consumption databases and reports published by governmental organizations. A PubMed search was conducted using keywords related to the selected group of drugs AND 'hospital drug utilization'. The data sources for hospital DU information varied widely and included 14 databases from 25 reviewed countries. Bulgaria, Croatia, Denmark, Estonia, Finland, France, Hungary, Iceland, Latvia, Norway and Sweden obtain information on inpatient DU at a national level from wholesalers/manufacturers. In Belgium, Italy and Portugal, drugs dispensed to patients in hospitals are registered at a national level. Data are freely available online only for Denmark and Iceland. From the PubMed search, of a total of 868 retrieved studies, only 13 studies used the ATC/DDD methodology. Although the number of DDD/100 bed-days was used in four studies, other units of measure were also used. The type of information provided for the inpatient sector allowed primarily for conducting DU research at an aggregated data level. The existence of national administrative structures to monitor hospital DU would contribute to promoting the rational use of medicines and improving the safety and quality of prescribing.
  • Quality of care in European home care programs using the second generation interRAI Home Care Quality Indicators (HCQIs).

    Foebel, Andrea D; van Hout, Hein P; van der Roest, Henriëtte G; Topinkova, Eva; Garms-Homolova, Vjenka; Frijters, Dinnus; Finne-Soveri, Harriet; Jónsson, Pálmi V; Hirdes, John P; Bernabei, Roberto; Onder, Graziano; [ 1 ] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden [ 2 ] Univ Cattolica Sacro Cuore, Dept Geriatr Neurosci & Orthoped, I-00168 Rome, Italy [ 3 ] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Dept Gen Practice & Elderly Care Med, Amsterdam, Netherlands [ 4 ] Charles Univ Prague, Fac Med 1, Dept Geriatr, Prague, Czech Republic [ 5 ] Univ Appl Sci Technol & Econ, HTW Berlin, Berlin, Germany [ 6 ] Natl Inst Hlth & Welf, Helsinki, Finland [ 7 ] Univ Iceland, Fac Med, Dept Geriatr, Reykjavik, Iceland [ 8 ] Univ Waterloo, Sch Publ Hlth & Hlth Syst, Waterloo, ON N2L 3G1, Canada (BioMed Central, 2015)
    Evaluating the quality of care provided to older individuals is a key step to ensure that needs are being met and to target interventions to improve care. To this aim, interRAI's second-generation home care quality indicators (HCQIs) were developed in 2013. This study assesses the quality of home care services in six European countries using these HCQIs as well as the two derived summary scales.
  • The Y-chromosome point mutation rate in humans.

    Helgason, Agnar; Einarsson, Axel W; Guðmundsdóttir, Valdís B; Sigurðsson, Ásgeir; Gunnarsdóttir, Ellen D; Jagadeesan, Anuradha; Ebenesersdóttir, S Sunna; Kong, Augustine; Stefánsson, Kári; Amgen Inc, DeCODE Genet, Reykjavik, Iceland, Univ Iceland, Dept Anthropol, Reykjavik, Iceland, Univ Iceland, Fac Med, Reykjavik, Iceland (Nature Publishing Group, 2015-05)
    Mutations are the fundamental source of biological variation, and their rate is a crucial parameter for evolutionary and medical studies. Here we used whole-genome sequence data from 753 Icelandic males, grouped into 274 patrilines, to estimate the point mutation rate for 21.3 Mb of male-specific Y chromosome (MSY) sequence, on the basis of 1,365 meioses (47,123 years). The combined mutation rate for 15.2 Mb of X-degenerate (XDG), X-transposed (XTR) and ampliconic excluding palindromes (rAMP) sequence was 8.71 × 10(-10) mutations per position per year (PPPY). We observed a lower rate (P = 0.04) of 7.37 × 10(-10) PPPY for 6.1 Mb of sequence from palindromes (PAL), which was not statistically different from the rate of 7.2 × 10(-10) PPPY for paternally transmitted autosomes. We postulate that the difference between PAL and the other MSY regions may provide an indication of the rate at which nascent autosomal and PAL de novo mutations are repaired as a result of gene conversion.

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