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

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Persistent URL dx.doi.org/10.1038/s41467-019-09860-0, hdl.handle.net/1765/117026
Journal Nature Communications
Citation
Styrkarsdottir, U, Stefansson, O. A., Gunnarsdottir, K., Thorleifsson, G, Lund, S.H., Stefansdottir, L., … Zwart, J-A. (2019). GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures. Nature Communications, 10. doi:10.1038/s41467-019-09860-0