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Genome-Wide Association Meta-Analysis of Cortical Bone Mineral Density Unravels Allelic Heterogeneity at the RANKL Locus and Potential Pleiotropic Effects on Bone

Author

Listed:
  • Lavinia Paternoster
  • Mattias Lorentzon
  • Liesbeth Vandenput
  • Magnus K Karlsson
  • Östen Ljunggren
  • Andreas Kindmark
  • Dan Mellstrom
  • John P Kemp
  • Caroline E Jarett
  • Jeff M P Holly
  • Adrian Sayers
  • Beate St. Pourcain
  • Nicholas J Timpson
  • Panos Deloukas
  • George Davey Smith
  • Susan M Ring
  • David M Evans
  • Jon H Tobias
  • Claes Ohlsson

Abstract

Previous genome-wide association (GWA) studies have identified SNPs associated with areal bone mineral density (aBMD). However, this measure is influenced by several different skeletal parameters, such as periosteal expansion, cortical bone mineral density (BMDC) cortical thickness, trabecular number, and trabecular thickness, which may be under distinct biological and genetic control. We have carried out a GWA and replication study of BMDC, as measured by peripheral quantitative computed tomography (pQCT), a more homogenous and valid measure of actual volumetric bone density. After initial GWA meta-analysis of two cohorts (ALSPAC n = 999, aged ∼15 years and GOOD n = 935, aged ∼19 years), we attempted to replicate the BMDC associations that had p

Suggested Citation

  • Lavinia Paternoster & Mattias Lorentzon & Liesbeth Vandenput & Magnus K Karlsson & Östen Ljunggren & Andreas Kindmark & Dan Mellstrom & John P Kemp & Caroline E Jarett & Jeff M P Holly & Adrian Sayers, 2010. "Genome-Wide Association Meta-Analysis of Cortical Bone Mineral Density Unravels Allelic Heterogeneity at the RANKL Locus and Potential Pleiotropic Effects on Bone," PLOS Genetics, Public Library of Science, vol. 6(11), pages 1-12, November.
    • Handle: RePEc:plo:pgen00:1001217
    DOI: 10.1371/journal.pgen.1001217
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    1. William J. Boyle & W. Scott Simonet & David L. Lacey, 2003. "Osteoclast differentiation and activation," Nature, Nature, vol. 423(6937), pages 337-342, May.
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