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  • Hsu, Y. H.Broad Institute,Harvard Medical School (author)

Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2019-03-19
  • Wiley,2019

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/282672
  • https://gup.ub.gu.se/publication/282672URI
  • https://doi.org/10.1002/jbmr.3698DOI
  • https://lup.lub.lu.se/record/0fdeb77b-c30c-4644-8564-14ee3a855e1eURI

Supplementary language notes

  • Language:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with similar to 2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p <= 2.6 x 10(-8)) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 x 10(-5)). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12% to 22% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility. (c) 2019 American Society for Bone and Mineral Research.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Estrada, K.Broad Institute,Erasmus University Medical Center (author)
  • Evangelou, E.University of Ioannina (author)
  • Ackert-Bicknell, C.University of Rochester (author)
  • Akesson, KristinaLund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)orto-kak (author)
  • Beck, T.Beck Radiological Innovations Inc (author)
  • Brown, S. J.Sir Charles Gairdner Hospital (author)
  • Capellini, T.Harvard University (author)
  • Carbone, L.Augusta University (author)
  • Cauley, J.University of Pittsburgh (author)
  • Cheung, C. L.University of Hong Kong (author)
  • Cummings, S. R.California Pacific Medical Center,Oslo university hospital,University of Oslo (author)
  • Czerwinski, S.University of Texas (author)
  • Demissie, S.Boston University,King's College London (author)
  • Econs, M.Indiana University (author)
  • Evans, D.California Pacific Medical Center (author)
  • Farber, C.University of Virginia (author)
  • Gautvik, K.University of Oslo (author)
  • Harris, T.National Institute on Aging, United States (author)
  • Kammerer, C.University of Pittsburgh (author)
  • Kemp, J.University of Bristol,University of Queensland (author)
  • Koller, D. L.Indiana University,University of Bristol (author)
  • Kung, A.University of Hong Kong (author)
  • Lawlor, D. (author)
  • Lee, M. (author)
  • Lorentzon, Mattias,1970Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Sahlgrenska Academy(Swepub:gu)xlomat (author)
  • McGuigan, FionaLund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups,University of Rochester(Swepub:lu)med-fam (author)
  • Medina-Gomez, C.Erasmus University Medical Center (author)
  • Mitchell, B.University of Maryland School of Medicine (author)
  • Newman, A.University of Pittsburgh (author)
  • Nielson, C.Oregon Health & Science University (author)
  • Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Sahlgrenska Academy(Swepub:gu)xohlcl (author)
  • Peacock, M.Indiana University (author)
  • Reppe, S. (author)
  • Richards, J. B. (author)
  • Robbins, J.University of California, Davis (author)
  • Sigurdsson, G.University of Iceland (author)
  • Spector, T. D. (author)
  • Stefansson, K.deCODE Genetics (author)
  • Streeten, E.University of Maryland School of Medicine (author)
  • Styrkarsdottir, U.deCODE Genetics (author)
  • Tobias, J.University of Bristol (author)
  • Trajanoska, K.Erasmus University Medical Center (author)
  • Uitterlinden, A.Erasmus University Medical Center (author)
  • Vandenput, Liesbeth,1974Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition,Sahlgrenska Academy(Swepub:gu)xvanli (author)
  • Wilson, S. G.King's College London,Sir Charles Gairdner Hospital,University of Western Australia, Crawley (author)
  • Yerges-Armstrong, L.GlaxoSmithKline (author)
  • Young, M.Harvard University (author)
  • Zillikens, M. C.Erasmus University Medical Center (author)
  • Rivadeneira, F.Erasmus University Medical Center (author)
  • Kiel, D. P.Broad Institute,Harvard Medical School (author)
  • Karasik, D.Bar-Ilan University (author)
  • Broad InstituteHarvard Medical School (creator_code:org_t)

Related titles

  • In:Journal of Bone and Mineral Research: Wiley34:7, s. 1284-12960884-04311523-4681

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