• Variant of TREM2 associated with the risk of Alzheimer's disease.

      Jonsson, Thorlakur; Stefansson, Hreinn; Steinberg, Stacy; Jonsdottir, Ingileif; Jonsson, Palmi V; Snaedal, Jon; Bjornsson, Sigurbjorn; Huttenlocher, Johanna; Levey, Allan I; Lah, James J; et al. (Massachusetts Medical Society, 2013-01-10)
      BACKGROUND: Sequence variants, including the ε4 allele of apolipoprotein E, have been associated with the risk of the common late-onset form of Alzheimer's disease. Few rare variants affecting the risk of late-onset Alzheimer's disease have been found. METHODS: We obtained the genome sequences of 2261 Icelanders and identified sequence variants that were likely to affect protein function. We imputed these variants into the genomes of patients with Alzheimer's disease and control participants and then tested for an association with Alzheimer's disease. We performed replication tests using case-control series from the United States, Norway, The Netherlands, and Germany. We also tested for a genetic association with cognitive function in a population of unaffected elderly persons. RESULTS: A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P=3.42×10(-10)). The mutation had a frequency of 0.46% in controls 85 years of age or older. We observed the association in additional sample sets (odds ratio, 2.90; 95% CI, 2.16 to 3.91; P=2.1×10(-12) in combined discovery and replication samples). We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer's disease had poorer cognitive function than noncarriers (P=0.003). CONCLUSIONS: Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease through impaired containment of inflammatory processes. (Funded by the National Institute on Aging and others.).
    • 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; et al. (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.
    • 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; et al. (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.
    • 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.
    • 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.