Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies

Fernando Rivadeneira; U Styrkarsdottir; Karol Estrada Gil; BV Halldorsson; YH Hsu; JB Richards; M.C. Zillikens; FK Kavvoura; Najaf Amin; YS Aulchenko; LA Cupples; P Deloukas; S Demissie; E Grundberg; Bert Hofman; A Kong; D Karasik; Joyce van Meurs; Ben Oostra; T Pastinen; Huib Pols; G Sigurdsson; N Soranzo; G Thorleifsson; U Thorsteinsdottir; FMK Williams; SG Wilson; YH Zhou; SH Ralston; Cornelia Duijn; T Spector; DP Kiel; K Stefansson; JPA Ioannidis; André Uitterlinden

doi:10.1038/ng.446

Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies

Fernando Rivadeneira, U Styrkarsdottir, Karol Estrada Gil, BV Halldorsson, YH Hsu, JB Richards, M.C. Zillikens, FK Kavvoura, Najaf Amin, YS Aulchenko, LA Cupples, P Deloukas, S Demissie, E Grundberg, Bert Hofman, A Kong, D Karasik, Joyce van Meurs, Ben Oostra, T PastinenHuib Pols, G Sigurdsson, N Soranzo, G Thorleifsson, U Thorsteinsdottir, FMK Williams, SG Wilson, YH Zhou, SH Ralston, Cornelia Duijn, T Spector, DP Kiel, K Stefansson, JPA Ioannidis, André Uitterlinden

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Abstract

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.

Original language	Undefined/Unknown
Pages (from-to)	1199-U58
Journal	Nature Genetics
Volume	41
Issue number	11
DOIs	https://doi.org/10.1038/ng.446
Publication status	Published - 2009

Research programs

EMC MGC-02-96-01
EMC MM-01-39-02
EMC NIHES-01-64-02

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10.1038/ng.446

http://hdl.handle.net/1765/24583

Cite this

Rivadeneira, F., Styrkarsdottir, U., Estrada Gil, K., Halldorsson, BV., Hsu, YH., Richards, JB., Zillikens, M. C., Kavvoura, FK., Amin, N., Aulchenko, YS., Cupples, LA., Deloukas, P., Demissie, S., Grundberg, E., Hofman, B., Kong, A., Karasik, D., van Meurs, J., Oostra, B., ... Uitterlinden, A. (2009). Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nature Genetics, 41(11), 1199-U58. https://doi.org/10.1038/ng.446

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abstract = "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.",

author = "Fernando Rivadeneira and U Styrkarsdottir and {Estrada Gil}, Karol and BV Halldorsson and YH Hsu and JB Richards and M.C. Zillikens and FK Kavvoura and Najaf Amin and YS Aulchenko and LA Cupples and P Deloukas and S Demissie and E Grundberg and Bert Hofman and A Kong and D Karasik and {van Meurs}, Joyce and Ben Oostra and T Pastinen and Huib Pols and G Sigurdsson and N Soranzo and G Thorleifsson and U Thorsteinsdottir and FMK Williams and SG Wilson and YH Zhou and SH Ralston and Cornelia Duijn and T Spector and DP Kiel and K Stefansson and JPA Ioannidis and Andr{\'e} Uitterlinden",

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Rivadeneira, F, Styrkarsdottir, U, Estrada Gil, K, Halldorsson, BV, Hsu, YH, Richards, JB, Zillikens, MC, Kavvoura, FK, Amin, N, Aulchenko, YS, Cupples, LA, Deloukas, P, Demissie, S, Grundberg, E, Hofman, B, Kong, A, Karasik, D, van Meurs, J, Oostra, B, Pastinen, T, Pols, H, Sigurdsson, G, Soranzo, N, Thorleifsson, G, Thorsteinsdottir, U, Williams, FMK, Wilson, SG, Zhou, YH, Ralston, SH, Duijn, C, Spector, T, Kiel, DP, Stefansson, K, Ioannidis, JPA & Uitterlinden, A 2009, 'Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies', Nature Genetics, vol. 41, no. 11, pp. 1199-U58. https://doi.org/10.1038/ng.446

TY - JOUR

T1 - Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies

AU - Rivadeneira, Fernando

AU - Styrkarsdottir, U

AU - Estrada Gil, Karol

AU - Halldorsson, BV

AU - Hsu, YH

AU - Richards, JB

AU - Zillikens, M.C.

AU - Kavvoura, FK

AU - Amin, Najaf

AU - Aulchenko, YS

AU - Cupples, LA

AU - Deloukas, P

AU - Demissie, S

AU - Grundberg, E

AU - Hofman, Bert

AU - Kong, A

AU - Karasik, D

AU - van Meurs, Joyce

AU - Oostra, Ben

AU - Pastinen, T

AU - Pols, Huib

AU - Sigurdsson, G

AU - Soranzo, N

AU - Thorleifsson, G

AU - Thorsteinsdottir, U

AU - Williams, FMK

AU - Wilson, SG

AU - Zhou, YH

AU - Ralston, SH

AU - Duijn, Cornelia

AU - Spector, T

AU - Kiel, DP

AU - Stefansson, K

AU - Ioannidis, JPA

AU - Uitterlinden, André

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1038/ng.446

DO - 10.1038/ng.446

M3 - Article

SN - 1061-4036

VL - 41

SP - 1199-U58

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -