Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture

2.50
Hdl Handle:
http://hdl.handle.net/2336/86558
Title:
Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture
Authors:
Richards, J Brent; Kavvoura, Fotini K; Rivadeneira, Fernando; Styrkarsdottir, Unnur; Estrada, Karol; Halldorsson, Bjarni V; Hsu, Yi-Hsiang; Zillikens, M Carola; Wilson, Scott G; Mullin, Benjamin H; Amin, Najaf; Aulchenko, Yurii S; Cupples, L Adrienne; Deloukas, Panagiotis; Demissie, Serkalem; Hofman, Albert; Kong, Augustine; Karasik, David; van Meurs, Joyce B; Oostra, Ben A; Pols, Huibert A P; Sigurdsson, Gunnar; Thorsteinsdottir, Unnur; Soranzo, Nicole; Williams, Frances M K; Zhou, Yanhua; Ralston, Stuart H; Thorleifsson, Gudmar; van Duijn, Cornelia M; Kiel, Douglas P; Stefansson, Kari; Uitterlinden, André G; Ioannidis, John P A; Spector, Tim D
Citation:
Ann. Intern. Med. 2009, 151(8):528-37
Issue Date:
20-Oct-2009
Abstract:
BACKGROUND: Osteoporosis is a highly heritable trait. Many candidate genes have been proposed as being involved in regulating bone mineral density (BMD). Few of these findings have been replicated in independent studies. OBJECTIVE: To assess the relationship between BMD and fracture and all common single-nucleotide polymorphisms (SNPs) in previously proposed osteoporosis candidate genes. DESIGN: Large-scale meta-analysis of genome-wide association data. SETTING: 5 international, multicenter, population-based studies. PARTICIPANTS: Data on BMD were obtained from 19 195 participants (14 277 women) from 5 populations of European origin. Data on fracture were obtained from a prospective cohort (n = 5974) from the Netherlands. MEASUREMENTS: Systematic literature review using the Human Genome Epidemiology Navigator identified autosomal genes previously evaluated for association with osteoporosis. We explored the common SNPs arising from the haplotype map of the human genome (HapMap) across all these genes. BMD at the femoral neck and lumbar spine was measured by dual-energy x-ray absorptiometry. Fractures were defined as clinically apparent, site-specific, validated nonvertebral and vertebral low-energy fractures. RESULTS: 150 candidate genes were identified and 36 016 SNPs in these loci were assessed. SNPs from 9 gene loci (ESR1, LRP4, ITGA1, LRP5, SOST, SPP1, TNFRSF11A, TNFRSF11B, and TNFSF11) were associated with BMD at either site. For most genes, no SNP was statistically significant. For statistically significant SNPs (n = 241), effect sizes ranged from 0.04 to 0.18 SD per allele. SNPs from the LRP5, SOST, SPP1, and TNFRSF11A loci were significantly associated with fracture risk; odds ratios ranged from 1.13 to 1.43 per allele. These effects on fracture were partially independent of BMD at SPP1 and SOST. Limitation: Only common polymorphisms in linkage disequilibrium with SNPs in HapMap could be assessed, and previously reported associations for SNPs in some candidate genes could not be excluded. CONCLUSION: In this large-scale collaborative genome-wide meta-analysis, 9 of 150 candidate genes were associated with regulation of BMD, 4 of which also significantly affected risk for fracture. However, most candidate genes had no consistent association with BMD.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://www.annals.org/content/151/8/528.abstract

Full metadata record

DC FieldValue Language
dc.contributor.authorRichards, J Brenten
dc.contributor.authorKavvoura, Fotini Ken
dc.contributor.authorRivadeneira, Fernandoen
dc.contributor.authorStyrkarsdottir, Unnuren
dc.contributor.authorEstrada, Karolen
dc.contributor.authorHalldorsson, Bjarni Ven
dc.contributor.authorHsu, Yi-Hsiangen
dc.contributor.authorZillikens, M Carolaen
dc.contributor.authorWilson, Scott Gen
dc.contributor.authorMullin, Benjamin Hen
dc.contributor.authorAmin, Najafen
dc.contributor.authorAulchenko, Yurii Sen
dc.contributor.authorCupples, L Adrienneen
dc.contributor.authorDeloukas, Panagiotisen
dc.contributor.authorDemissie, Serkalemen
dc.contributor.authorHofman, Alberten
dc.contributor.authorKong, Augustineen
dc.contributor.authorKarasik, Daviden
dc.contributor.authorvan Meurs, Joyce Ben
dc.contributor.authorOostra, Ben Aen
dc.contributor.authorPols, Huibert A Pen
dc.contributor.authorSigurdsson, Gunnaren
dc.contributor.authorThorsteinsdottir, Unnuren
dc.contributor.authorSoranzo, Nicoleen
dc.contributor.authorWilliams, Frances M Ken
dc.contributor.authorZhou, Yanhuaen
dc.contributor.authorRalston, Stuart Hen
dc.contributor.authorThorleifsson, Gudmaren
dc.contributor.authorvan Duijn, Cornelia Men
dc.contributor.authorKiel, Douglas Pen
dc.contributor.authorStefansson, Karien
dc.contributor.authorUitterlinden, André Gen
dc.contributor.authorIoannidis, John P Aen
dc.contributor.authorSpector, Tim Den
dc.date.accessioned2009-11-20T11:01:12Z-
dc.date.available2009-11-20T11:01:12Z-
dc.date.issued2009-10-20-
dc.date.submitted2009-11-20-
dc.identifier.citationAnn. Intern. Med. 2009, 151(8):528-37en
dc.identifier.issn1539-3704-
dc.identifier.pmid19841454-
dc.identifier.urihttp://hdl.handle.net/2336/86558-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractBACKGROUND: Osteoporosis is a highly heritable trait. Many candidate genes have been proposed as being involved in regulating bone mineral density (BMD). Few of these findings have been replicated in independent studies. OBJECTIVE: To assess the relationship between BMD and fracture and all common single-nucleotide polymorphisms (SNPs) in previously proposed osteoporosis candidate genes. DESIGN: Large-scale meta-analysis of genome-wide association data. SETTING: 5 international, multicenter, population-based studies. PARTICIPANTS: Data on BMD were obtained from 19 195 participants (14 277 women) from 5 populations of European origin. Data on fracture were obtained from a prospective cohort (n = 5974) from the Netherlands. MEASUREMENTS: Systematic literature review using the Human Genome Epidemiology Navigator identified autosomal genes previously evaluated for association with osteoporosis. We explored the common SNPs arising from the haplotype map of the human genome (HapMap) across all these genes. BMD at the femoral neck and lumbar spine was measured by dual-energy x-ray absorptiometry. Fractures were defined as clinically apparent, site-specific, validated nonvertebral and vertebral low-energy fractures. RESULTS: 150 candidate genes were identified and 36 016 SNPs in these loci were assessed. SNPs from 9 gene loci (ESR1, LRP4, ITGA1, LRP5, SOST, SPP1, TNFRSF11A, TNFRSF11B, and TNFSF11) were associated with BMD at either site. For most genes, no SNP was statistically significant. For statistically significant SNPs (n = 241), effect sizes ranged from 0.04 to 0.18 SD per allele. SNPs from the LRP5, SOST, SPP1, and TNFRSF11A loci were significantly associated with fracture risk; odds ratios ranged from 1.13 to 1.43 per allele. These effects on fracture were partially independent of BMD at SPP1 and SOST. Limitation: Only common polymorphisms in linkage disequilibrium with SNPs in HapMap could be assessed, and previously reported associations for SNPs in some candidate genes could not be excluded. CONCLUSION: In this large-scale collaborative genome-wide meta-analysis, 9 of 150 candidate genes were associated with regulation of BMD, 4 of which also significantly affected risk for fracture. However, most candidate genes had no consistent association with BMD.en
dc.language.isoenen
dc.publisherAmerican College of Physicians--American Society of Internal Medicineen
dc.relation.urlhttp://www.annals.org/content/151/8/528.abstracten
dc.subject.meshBone Densityen
dc.subject.meshFemaleen
dc.subject.meshFractures, Boneen
dc.subject.meshGenotypeen
dc.subject.meshHumansen
dc.subject.meshLinkage Disequilibriumen
dc.subject.meshMaleen
dc.subject.meshOsteoporosisen
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshProspective Studiesen
dc.subject.meshRisk Factorsen
dc.titleCollaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fractureen
dc.typeArticleen
dc.contributor.departmentMcGill University, Montreal, Quebec, Canada.en
dc.identifier.journalAnnals of internal medicineen

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