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

Ling Oei, Karol Estrada, Emma L. Duncan, Claus Christiansen, Ching-Ti Liu, Bente L. Langdahl, Barbara Obermayer-Pietsch, Jose A. Riancho, Richard L. Prince, Natasja M. van Schoor, Eugene McCloskey, Yi-Hsiang Hsu, Evangelos Evangelou, Evangelia Ntzani, David M. Evans, Nerea Alonso, Lise B. Husted, Carmen Valero, Jose L. Hernandez, Joshua R. LewisStephen K. Kaptoge, Kun Zhu, L. Adrienne Cupples, Carolina Medina-Gomez, Liesbeth Vandenput, Ghi Su Kim, Seung Hun Lee, Martha C. Castano-Betancourt, Edwin H. G. Oei, Josefina Martinez, Anna Daroszewska, Marjolein van der Klift, Dan Mellstrom, Lizbeth Herrera, Magnus K. Karlsson, Albert Hofman, Osten Ljunggren, Huibert A. P. Pols, Lisette Stolk, Joyce B. J. van Meurs, John P. A. Ioannidis, M. Carola Zillikens, Paul Lips, David Karasik, Andre G. Uitterlinden, Unnur Styrkarsdottir, Matthew A. Brown, Jung-Min Koh, J. Brent Richards, Jonathan Reeve, Claes Ohlsson, Stuart H. Ralston, Douglas P. Kiel, Fernando Rivadeneira*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fracture 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 >55 years; 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 p1.25) may still be consistent with an effect size

Original languageEnglish
Pages (from-to)20-27
Number of pages8
JournalBone
Volume59
DOIs
Publication statusPublished - Feb 2014

Keywords / Materials (for Non-textual outputs)

  • Genome-wide association study
  • Vertebral fracture risk
  • Genetics of osteoporosis
  • GEFOS consortium
  • FOXC2
  • BONE-MINERAL DENSITY
  • QUALITY-OF-LIFE
  • EUROPEAN PROSPECTIVE OSTEOPOROSIS
  • POSTMENOPAUSAL WOMEN
  • GEELONG-OSTEOPOROSIS
  • TURNOVER MARKERS
  • CAMARGO COHORT
  • ELDERLY-WOMEN
  • DOUBLE-BLIND
  • MEN

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