Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus

L. Oei, K. Estrada, E.L. Duncan, C. Christiansen, C.T. Liu, B.L. Langdahl, B. Obermayer-Pietsch, J.A. Riancho, R.L. Prince, N.M. van Schoor, E. McCloskey, Y.H. Hsu, E. Evangelou, E. Ntzani, D.M. Evans, N. Alonso, L.B. Husted, C. Valero, J.L. Hernandez, J.R. LewisS.K. Kaptoge, K. Zhu, L.A. Cupples, C. Medina-Gomez, L. Vandenput, G.S. Kim, S.H. Lee, M.C. Castano-Betancourt, E.H.G. Oei, J. Martinez, A. Daroszewska, M. van der Klift, D. Mellstrom, L Herrera, M.K. Karlsson, A. Hofman, O. Ljunggren, H.A.P. Pols, L. Stolk, J.B.J. van Meurs, J.P.A. Ioannidis, M.C. Zillikens, P.T.A.M. Lips, D. Karasik, A. G. Uitterlinden, U. Styrkarsdottir, M. A. Brown, J.M. Koh, J.B. Richards, J. Reeve, C. Ohlsson, S.H. Ralston, D.P. Kiel, F. Rivadeneira

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Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p<5×10
Original languageEnglish
Pages (from-to)20-27
Publication statusPublished - 2014

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