4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 10, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-09860-0

Keywords

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Funding

  1. Arthritis Research UK [18030]
  2. [23359]
  3. ESRC [ES/S008349/1] Funding Source: UKRI
  4. MRC [MR/N01104X/1, MR/N01104X/2, G1001799, MR/P020941/1] Funding Source: UKRI

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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 x 10(-42), beta = -0.090) and confers risk of hip fracture (P = 1.0 x 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.

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