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Styrkarsdottir, U.* ; Stefansson, O.A.* ; Gunnarsdottir, K.* ; Thorleifsson, G.* ; Lund, S.H.* ; Stefansdottir, L.* ; Juliusson, K.* ; Agustsdottir, A.B.* ; Zink, F.* ; Halldorsson, G.H.* ; Ivarsdottir, E.V.* ; Benonisdottir, S.* ; Jonsson, H.* ; Gylfason, A.* ; Norland, K.* ; Trajanoska, K.* ; Boer, C.G.* ; Southam, L.* ; Leung, J.C.S.* ; Tang, N.L.S.* ; Kwok, T.C.Y.* ; Lee, J.S.W.* ; Ho, S.C.* ; Byrjalsen, I.* ; Center, J.R.* ; Lee, S.H.* ; Koh, J.M.* ; Lohmander, L.S.* ; Ho-Pham, L.T.* ; Nguyen, T.V.* ; Eisman, J.A.* ; Woo, J.* ; Leung, P.C.* ; Loughlin, J.* ; Zeggini, E. ; Christiansen, C.* ; Rivadeneira, F.* ; van Meurs, J.* ; Uitterlinden, A.G.* ; Mogensen, B.* ; Ingvarsson, T.* ; Sigurdsson, G.* ; Benediktsson, R.* ; Sulem, P.* ; Jonsdottir, I.* ; Masson, G.* ; Holm, H.* ; Norddahl, G.L.* ; Thorsteinsdottir, U.* ; Gudbjartsson, D.F.* ; Stefansson, K.*

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

Nat. Commun. 10:2054 (2019)

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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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