GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures

Nat Commun. 2019 May 3;10(1):2054. doi: 10.1038/s41467-019-09860-0.

Abstract

Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 - 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10-42, β = -0.090) and confers risk of hip fracture (P = 1.0 × 10-8, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Body Height / genetics
  • Bone Density / genetics*
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / physiology
  • Case-Control Studies
  • Collagen Type XI / genetics
  • Female
  • Follow-Up Studies
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Growth Differentiation Factor 5 / genetics
  • Hip Fractures / epidemiology
  • Hip Fractures / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Osteoarthritis / epidemiology
  • Osteoarthritis / genetics*
  • Risk Factors

Substances

  • COL11A1 protein, human
  • Collagen Type XI
  • GDF5 protein, human
  • Growth Differentiation Factor 5
  • MIRN196 microRNA, human
  • MicroRNAs