Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- Estrada, K.
- Styrkarsdottir, U.
- Evangelou, E.
- Hsu, Y.H.
- Duncan, E.L.
- Ntzani, E.E.
- Oei, L.
- Albagha, O.M.
- Amin, N.
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- Mellström, D.
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- Pettersson-Kymmer, U.
- Reid, D.M.
- Riancho, J.A.
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- Raychaudhuri, S.
- Cauley, J.A.
- Chasman, D.I.
- Clark, G.R.
- Cummings, S.R.
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- Hofman, A.
- Jackson, R.D.
- Jones, G.
- Jukema, J.W.
- Khaw, K.T.
- Lehtimäki, T.
- Liu, Y.
- Lorentzon, M.
- McCloskey, E.
- Mitchell, B.D.
- Nandakumar, K.
- Nicholson, G.C.
- Oostra, B.A.
- Peacock, M.
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- Prince, R.L.
- Raitakari, O.
- Reid, I.R.
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- Shuldiner, A.R.
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- van Duijn, C.M.
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- Streeten, E.A.
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- Thorsteinsdottir, U.
- Ohlsson, C.
- Karasik, D.
- Richards, J.B.
- Brown, M.A.
- Stefansson, K.
- Uitterlinden, A.G.
- Ralston, S.H.
- Ioannidis, J.P.
- Kiel, D.P.
- Rivadeneira, F.
DOIAbstract
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we...
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