Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies
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Authors
Rivadeneira, FernandoStyrkarsdottir, Unnur
Estrada, Karol
Halldorsson, Bjarni V
Hsu, Yi-Hsiang
Richards, J Brent
Zillikens, M Carola
Kavvoura, Fotini K
Amin, Najaf
Aulchenko, Yurii S
Cupples, L Adrienne
Deloukas, Panagiotis
Demissie, Serkalem
Grundberg, Elin
Hofman, Albert
Kong, Augustine
Karasik, David
van Meurs, Joyce B
Oostra, Ben
Pastinen, Tomi
Pols, Huibert A P
Sigurdsson, Gunnar
Soranzo, Nicole
Thorleifsson, Gudmar
Thorsteinsdottir, Unnur
Williams, Frances M K
Wilson, Scott G
Zhou, Yanhua
Ralston, Stuart H
van Duijn, Cornelia M
Spector, Timothy
Kiel, Douglas P
Stefansson, Kari
Ioannidis, John P A
Uitterlinden, André G
Issue Date
2009-11-01
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Nat. Genet. 2009, 41(11):1199-206Abstract
Bone mineral density (BMD) is a heritable complex trait used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. We performed meta-analysis of five genome-wide association studies of femoral neck and lumbar spine BMD in 19,195 subjects of Northern European descent. We identified 20 BMD loci that reached genome-wide significance (GWS; P < 5 x 10(-8)), of which 13 map to regions not previously associated with this trait: 1p31.3 (GPR177), 2p21 (SPTBN1), 3p22 (CTNNB1), 4q21.1 (MEPE), 5q14 (MEF2C), 7p14 (STARD3NL), 7q21.3 (FLJ42280), 11p11.2 (LRP4, ARHGAP1, F2), 11p14.1 (DCDC5), 11p15 (SOX6), 16q24 (FOXL1), 17q21 (HDAC5) and 17q12 (CRHR1). The meta-analysis also confirmed at GWS level seven known BMD loci on 1p36 (ZBTB40), 6q25 (ESR1), 8q24 (TNFRSF11B), 11q13.4 (LRP5), 12q13 (SP7), 13q14 (TNFSF11) and 18q21 (TNFRSF11A). The many SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism and highlight the complex genetic architecture that underlies osteoporosis and variation in BMD.Description
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http://dx.doi.org/10.1038/ng.446ae974a485f413a2113503eed53cd6c53
10.1038/ng.446
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