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

F. Rivadeneira, U. Styrakarsdottir, K. Estrada, B.V. Halldorsson, Y.H. Hsu, J.B. Richards, M.C. Zillikens, F.K. Kavvoura, N. Amin, Y.S. Aulchenko, L.A. Cupples, P. Deloukas, S. Demissie, E. Grundberg, A. Hofman, A. Kong, D. Karasik, J.B. Van Meurs, B. Oostra, T. Pastinen & 15 others H.A.P. Pols, G. Sigurdsson, N. Soranzo, G. Thorleifsson, U. Thorsteinsdottir, M.K. Williams F, Scott Wilson, Y. Zhou, S.H. Ralston, C.M. Van Duijn, T. Spector, D.P. Kiel, K. Stefansson, J.P.A. Ioannidis, A.G. Uitterlinden

Research output: Contribution to journalArticle

475 Citations (Scopus)

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 × 10^sup -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. [PUBLICATION ABSTRACT]
Original languageEnglish
Pages (from-to)1191-1206
JournalNature Genetics
Volume41
Issue number11
DOIs
Publication statusPublished - 2009

Fingerprint

Genome-Wide Association Study
Bone Density
Meta-Analysis
Osteoporosis
Femur Neck
Single Nucleotide Polymorphism
Spine
Genome
Bone and Bones
Genes

Cite this

Rivadeneira, F., Styrakarsdottir, U., Estrada, K., Halldorsson, B. V., Hsu, Y. H., Richards, J. B., ... Uitterlinden, A. G. (2009). Twenty bone mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nature Genetics, 41(11), 1191-1206. https://doi.org/10.1038/ng.446
Rivadeneira, F. ; Styrakarsdottir, U. ; Estrada, K. ; Halldorsson, B.V. ; Hsu, Y.H. ; Richards, J.B. ; Zillikens, M.C. ; Kavvoura, F.K. ; Amin, N. ; Aulchenko, Y.S. ; Cupples, L.A. ; Deloukas, P. ; Demissie, S. ; Grundberg, E. ; Hofman, A. ; Kong, A. ; Karasik, D. ; Van Meurs, J.B. ; Oostra, B. ; Pastinen, T. ; Pols, H.A.P. ; Sigurdsson, G. ; Soranzo, N. ; Thorleifsson, G. ; Thorsteinsdottir, U. ; Williams F, M.K. ; Wilson, Scott ; Zhou, Y. ; Ralston, S.H. ; Van Duijn, C.M. ; Spector, T. ; Kiel, D.P. ; Stefansson, K. ; Ioannidis, J.P.A. ; Uitterlinden, A.G. / Twenty bone mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. In: Nature Genetics. 2009 ; Vol. 41, No. 11. pp. 1191-1206.
@article{16e910cbe2f14e02bfc86a6e345035dc,
title = "Twenty bone mineral-density loci identified by large-scale meta-analysis of genome-wide association studies",
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 × 10^sup -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. [PUBLICATION ABSTRACT]",
author = "F. Rivadeneira and U. Styrakarsdottir and K. Estrada and B.V. Halldorsson and Y.H. Hsu and J.B. Richards and M.C. Zillikens and F.K. Kavvoura and N. Amin and Y.S. Aulchenko and L.A. Cupples and P. Deloukas and S. Demissie and E. Grundberg and A. Hofman and A. Kong and D. Karasik and {Van Meurs}, J.B. and B. Oostra and T. Pastinen and H.A.P. Pols and G. Sigurdsson and N. Soranzo and G. Thorleifsson and U. Thorsteinsdottir and {Williams F}, M.K. and Scott Wilson and Y. Zhou and S.H. Ralston and {Van Duijn}, C.M. and T. Spector and D.P. Kiel and K. Stefansson and J.P.A. Ioannidis and A.G. Uitterlinden",
year = "2009",
doi = "10.1038/ng.446",
language = "English",
volume = "41",
pages = "1191--1206",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group - Macmillan Publishers",
number = "11",

}

Rivadeneira, F, Styrakarsdottir, U, Estrada, K, Halldorsson, BV, Hsu, YH, Richards, JB, Zillikens, MC, Kavvoura, FK, Amin, N, Aulchenko, YS, Cupples, LA, Deloukas, P, Demissie, S, Grundberg, E, Hofman, A, Kong, A, Karasik, D, Van Meurs, JB, Oostra, B, Pastinen, T, Pols, HAP, Sigurdsson, G, Soranzo, N, Thorleifsson, G, Thorsteinsdottir, U, Williams F, MK, Wilson, S, Zhou, Y, Ralston, SH, Van Duijn, CM, Spector, T, Kiel, DP, Stefansson, K, Ioannidis, JPA & Uitterlinden, AG 2009, 'Twenty bone mineral-density loci identified by large-scale meta-analysis of genome-wide association studies' Nature Genetics, vol. 41, no. 11, pp. 1191-1206. https://doi.org/10.1038/ng.446

Twenty bone mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. / Rivadeneira, F.; Styrakarsdottir, U.; Estrada, K.; Halldorsson, B.V.; Hsu, Y.H.; Richards, J.B.; Zillikens, M.C.; Kavvoura, F.K.; Amin, N.; Aulchenko, Y.S.; Cupples, L.A.; Deloukas, P.; Demissie, S.; Grundberg, E.; Hofman, A.; Kong, A.; Karasik, D.; Van Meurs, J.B.; Oostra, B.; Pastinen, T.; Pols, H.A.P.; Sigurdsson, G.; Soranzo, N.; Thorleifsson, G.; Thorsteinsdottir, U.; Williams F, M.K.; Wilson, Scott; Zhou, Y.; Ralston, S.H.; Van Duijn, C.M.; Spector, T.; Kiel, D.P.; Stefansson, K.; Ioannidis, J.P.A.; Uitterlinden, A.G.

In: Nature Genetics, Vol. 41, No. 11, 2009, p. 1191-1206.

Research output: Contribution to journalArticle

TY - JOUR

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

AU - Rivadeneira, F.

AU - Styrakarsdottir, U.

AU - Estrada, K.

AU - Halldorsson, B.V.

AU - Hsu, Y.H.

AU - Richards, J.B.

AU - Zillikens, M.C.

AU - Kavvoura, F.K.

AU - Amin, N.

AU - Aulchenko, Y.S.

AU - Cupples, L.A.

AU - Deloukas, P.

AU - Demissie, S.

AU - Grundberg, E.

AU - Hofman, A.

AU - Kong, A.

AU - Karasik, D.

AU - Van Meurs, J.B.

AU - Oostra, B.

AU - Pastinen, T.

AU - Pols, H.A.P.

AU - Sigurdsson, G.

AU - Soranzo, N.

AU - Thorleifsson, G.

AU - Thorsteinsdottir, U.

AU - Williams F, M.K.

AU - Wilson, Scott

AU - Zhou, Y.

AU - Ralston, S.H.

AU - Van Duijn, C.M.

AU - Spector, T.

AU - Kiel, D.P.

AU - Stefansson, K.

AU - Ioannidis, J.P.A.

AU - Uitterlinden, A.G.

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 × 10^sup -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. [PUBLICATION ABSTRACT]

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 × 10^sup -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. [PUBLICATION ABSTRACT]

U2 - 10.1038/ng.446

DO - 10.1038/ng.446

M3 - Article

VL - 41

SP - 1191

EP - 1206

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 11

ER -

Rivadeneira F, Styrakarsdottir U, Estrada K, Halldorsson BV, Hsu YH, Richards JB et al. Twenty bone mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nature Genetics. 2009;41(11):1191-1206. https://doi.org/10.1038/ng.446