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

Abstract

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.