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dc.contributor.authorLiu, Ching-Ti
dc.contributor.authorEstrada, Karol
dc.contributor.authorYerges-Armstrong, Laura M
dc.contributor.authorAmin, Najaf
dc.contributor.authorEvangelou, Evangelos
dc.contributor.authorLi, Guo
dc.contributor.authorMinster, Ryan L
dc.contributor.authorCarless, Melanie A
dc.contributor.authorKammerer, Candace M
dc.contributor.authorOei, Ling
dc.contributor.authorZhou, Yanhua
dc.contributor.authorAlonso, Nerea
dc.contributor.authorDailiana, Zoe
dc.contributor.authorEriksson, Joel
dc.contributor.authorGarcía-Giralt, Natalia
dc.contributor.authorGiroux, Sylvie
dc.contributor.authorHusted, Lise Bjerre
dc.contributor.authorKhusainova, Rita I
dc.contributor.authorKoromila, Theodora
dc.contributor.authorKung, Annie Waichee
dc.contributor.authorLewis, Joshua R
dc.contributor.authorMasi, Laura
dc.contributor.authorMencej-Bedrac, Simona
dc.contributor.authorNogues, Xavier
dc.contributor.authorPatel, Millan S
dc.contributor.authorPrezelj, Janez
dc.contributor.authorRichards, J Brent
dc.contributor.authorSham, Pak Chung
dc.contributor.authorSpector, Timothy
dc.contributor.authorVandenput, Liesbeth
dc.contributor.authorXiao, Su-Mei
dc.contributor.authorZheng, Hou-Feng
dc.contributor.authorZhu, Kun
dc.contributor.authorBalcells, Susana
dc.contributor.authorBrandi, Maria Luisa
dc.contributor.authorFrost, Morten
dc.contributor.authorGoltzman, David
dc.contributor.authorGonzález-Macías, Jesús
dc.contributor.authorKarlsson, Magnus
dc.contributor.authorKhusnutdinova, Elza K
dc.contributor.authorKollia, Panagoula
dc.contributor.authorLangdahl, Bente Lomholt
dc.contributor.authorLjunggren, Osten
dc.contributor.authorLorentzon, Mattias
dc.contributor.authorMarc, Janja
dc.contributor.authorMellström, Dan
dc.contributor.authorOhlsson, Claes
dc.contributor.authorOlmos, José M
dc.contributor.authorRalston, Stuart H
dc.contributor.authorRiancho, José A
dc.contributor.authorRousseau, François
dc.contributor.authorUrreizti, Roser
dc.contributor.authorVan Hul, Wim
dc.contributor.authorZarrabeitia, María T
dc.contributor.authorCastano-Betancourt, Martha
dc.contributor.authorDemissie, Serkalem
dc.contributor.authorGrundberg, Elin
dc.contributor.authorHerrera, Lizbeth
dc.contributor.authorKwan, Tony
dc.contributor.authorMedina-Gómez, Carolina
dc.contributor.authorPastinen, Tomi
dc.contributor.authorSigurdsson, Gunnar
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorVanmeurs, Joyce Bj
dc.contributor.authorBlangero, John
dc.contributor.authorHofman, Albert
dc.contributor.authorLiu, Yongmei
dc.contributor.authorMitchell, Braxton D
dc.contributor.authorO'Connell, Jeffrey R
dc.contributor.authorOostra, Ben A
dc.contributor.authorRotter, Jerome I
dc.contributor.authorStefansson, Kari
dc.contributor.authorStreeten, Elizabeth A
dc.contributor.authorStyrkarsdottir, Unnur
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorTylavsky, Frances A
dc.contributor.authorUitterlinden, Andre
dc.contributor.authorCauley, Jane A
dc.contributor.authorHarris, Tamara B
dc.contributor.authorIoannidis, John Pa
dc.contributor.authorPsaty, Bruce M
dc.contributor.authorRobbins, John A
dc.contributor.authorZillikens, M Carola
dc.contributor.authorVanduijn, Cornelia M
dc.contributor.authorPrince, Richard L
dc.contributor.authorKarasik, David
dc.contributor.authorRivadeneira, Fernando
dc.contributor.authorKiel, Douglas P
dc.contributor.authorCupples, L Adrienne
dc.contributor.authorHsu, Yi-Hsiang
dc.date.accessioned2013-09-02T11:06:38Z
dc.date.available2013-09-02T11:06:38Z
dc.date.issued2012-10
dc.date.submitted2013-09-02
dc.identifier.citationJ. Bone Miner. Res. 2012, 27(10):2051-64en_GB
dc.identifier.issn1523-4681
dc.identifier.pmid22692763
dc.identifier.doi10.1002/jbmr.1679
dc.identifier.urihttp://hdl.handle.net/2336/300627
dc.descriptionTo access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractSexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.
dc.description.sponsorshipMedtronic NIH R01 AG18728 R01HL088119 R01AR046838 U01 HL084756 R01 AR43351 P01-HL45522 R01-MH-078111 R01-MH-083824 Nutrition and Obesity Research Center of Maryland P30DK072488 NIAMS/NIH F32AR059469 Instituto de Salud Carlos III-FIS (Spanish Health Ministry) PI 06/0034 PI08/0183 Canadian Institutes of Health Research (CIHR) NHLBI HHSN268201200036C N01-HC-85239 N01-HC-85079 N01-HC-85086 N01-HC-35129 N01 HC15103 N01 HC-55222 N01-HC-75150 N01-HC-45133 HL080295 HL087652 HL105756 NIA AG-023629 AG-15928 AG-20098 AG-027058 N01AG62101 N01AG62103 N01AG62106 1R01AG032098-01A1 National Center of Advancing Translational Technologies CTSI UL1TR000124 National Institute of Diabetes and Digestive and Kidney Diseases DK063491 EUROSPAN (European Special Populations Research Network) European Commission FP6 STRP grant 018947 LSHG-CT-2006-01947 Netherlands Organisation for Scientific Research Erasmus MC Centre for Medical Systems Biology (CMSB) Netherlands Brain Foundation (HersenStichting Nederland) US National Institute for Arthritis, Musculoskeletal and Skin Diseases National Institute on Aging R01 AR/AG41398 R01 AR050066 R21 AR056405 National Heart, Lung, and Blood Institute's Framingham Heart Study N01-HC-25195 Affymetrix, Inc. N02-HL-6-4278 Canadian Institutes of Health Research from Institute of Aging 165446 Institute of Genetics 179433 Institute of Musculoskeletal health 221765 Intramural Research Program of the NIH, National Institute on Aging National Institutes of Health HHSN268200782096C Hong Kong Research Grant Council HKU 768610M Bone Health Fund of HKU Foundation KC Wong Education Foundation Small Project Funding 201007176237 Matching Grant CRCG Grant Osteoporosis and Endocrine Research Fund Genomics Strategic Research Theme of The University of Hong Kong Netherlands Organisation of Scientific Research NWO Investments 175.010.2005.011 911-03-012 Research Institute for Diseases in the Elderly 014-93-015 Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) 050-060-810 Erasmus Medical Center and Erasmus University, Rotterdam Netherlands Organization for the Health Research and Development (ZonMw) Research Institute for Diseases in the Elderly (RIDE) Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports European Commission (DG XII) Municipality of Rotterdam German Bundesministerium fur Forschung und Technology 01 AK 803 A-H 01 IG 07015 Gen_GB
dc.language.isoenen
dc.publisherWiley-Blackwellen_GB
dc.relation.urlhttp://dx.doi.org/10.1002/jbmr.1679en_GB
dc.rightsArchived with thanks to Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Researchen_GB
dc.subject.meshBone Densityen_GB
dc.subject.meshCohort Studiesen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGenesen_GB
dc.subject.meshGenome-Wide Association Studyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMeta-Analysis as Topicen_GB
dc.subject.meshPolymorphism, Single Nucleotideen_GB
dc.subject.meshQuantitative Trait Locien_GB
dc.subject.meshReproducibility of Resultsen_GB
dc.subject.meshSex Characteristicsen_GB
dc.titleAssessment of gene-by-sex interaction effect on bone mineral density.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biostatistics, Boston University School of Public Health, 801 Massachusetts Avenue CT3, Boston,MA 02118, USA.en_GB
dc.identifier.journalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Researchen_GB
dc.rights.accessOpen Access - Opinn aðganguren
html.description.abstractSexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. © 2012 American Society for Bone and Mineral Research.


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