A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus

L. Oei; Y.H. Hsu; U. Styrkarsdottir; B.H. Eussen; A. Klein; M.J. Peters; B. Halldorsson; C.T. Liu; N. Alonso; S.K. Kaptoge; G. Thorleifsson; G. Hallmans; L.J. Hocking; L.B. Husted; K.A. Jameson; M. Kruk; J.R. Lewis; M.S. Patel; S. Scollen; O. Svensson; S. Trompet; N.M. van Schoor; K. Zhu; B.M. Buckley; C. Cooper; I. Ford; D. Goltzman; J. Gonzalez-Macias; B.L. Langdahl; W.D. Leslie; P.T.A.M. Lips; R.S. Lorenc; J.M. Olmos; U. Pettersson-Kymmer; D.M. Reid; J.A. Riancho; P.E. Slagboom; C. Garcia-Ibarbia; T. Ingvarsson; H. Johannsdottir; R. Luben; C. Medina-Gomez; P. Arp; K. Nandakumar; S.T. Palsson; G. Sigurdsson; J.B.J. van Meurs; Y.H. Zhou; A. Hofman; J.W. Jukema; H.A.P. Pols; R.L. Prince; L.A. Cupples; C.R. Marshall; D. Pinto; D. Sato; S.W. Scherer; J. Reeve; U. Thorsteinsdottir; D. Karasik; J.B. Richards; K. Stefansson; A. G. Uitterlinden; S.H. Ralston; J.P.A. Ioannidis; D.P. Kiel; F. Rivadeneira; K. Estrada

doi:https://doi.org/10.1136/jmedgenet-2013-102064

A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus

L. Oei, Y.H. Hsu, U. Styrkarsdottir, B.H. Eussen, A. Klein, M.J. Peters, B. Halldorsson, C.T. Liu, N. Alonso, S.K. Kaptoge, G. Thorleifsson, G. Hallmans, L.J. Hocking, L.B. Husted, K.A. Jameson, M. Kruk, J.R. Lewis, M.S. Patel, S. Scollen, O. SvenssonS. Trompet, N.M. van Schoor, K. Zhu, B.M. Buckley, C. Cooper, I. Ford, D. Goltzman, J. Gonzalez-Macias, B.L. Langdahl, W.D. Leslie, P.T.A.M. Lips, R.S. Lorenc, J.M. Olmos, U. Pettersson-Kymmer, D.M. Reid, J.A. Riancho, P.E. Slagboom, C. Garcia-Ibarbia, T. Ingvarsson, H. Johannsdottir, R. Luben, C. Medina-Gomez, P. Arp, K. Nandakumar, S.T. Palsson, G. Sigurdsson, J.B.J. van Meurs, Y.H. Zhou, A. Hofman, J.W. Jukema, H.A.P. Pols, R.L. Prince, L.A. Cupples, C.R. Marshall, D. Pinto, D. Sato, S.W. Scherer, J. Reeve, U. Thorsteinsdottir, D. Karasik, J.B. Richards, K. Stefansson, A. G. Uitterlinden, S.H. Ralston, J.P.A. Ioannidis, D.P. Kiel, F. Rivadeneira, K. Estrada

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Abstract

Background Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk. Aim To identify CNVs associated with osteoporotic bone fracture risk. Method We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies. Results A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10

Original language	English
Pages (from-to)	122-131
Journal	Journal of medical genetics
Volume	51
Issue number	2
DOIs	https://doi.org/10.1136/jmedgenet-2013-102064
Publication status	Published - 2014

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Cite this

Oei, L., Hsu, Y. H., Styrkarsdottir, U., Eussen, B. H., Klein, A., Peters, M. J., Halldorsson, B., Liu, C. T., Alonso, N., Kaptoge, S. K., Thorleifsson, G., Hallmans, G., Hocking, L. J., Husted, L. B., Jameson, K. A., Kruk, M., Lewis, J. R., Patel, M. S., Scollen, S., ... Estrada, K. (2014). A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus. Journal of medical genetics, 51(2), 122-131. https://doi.org/10.1136/jmedgenet-2013-102064

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title = "A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus",

abstract = "Background Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk. Aim To identify CNVs associated with osteoporotic bone fracture risk. Method We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies. Results A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10",

author = "L. Oei and Y.H. Hsu and U. Styrkarsdottir and B.H. Eussen and A. Klein and M.J. Peters and B. Halldorsson and C.T. Liu and N. Alonso and S.K. Kaptoge and G. Thorleifsson and G. Hallmans and L.J. Hocking and L.B. Husted and K.A. Jameson and M. Kruk and J.R. Lewis and M.S. Patel and S. Scollen and O. Svensson and S. Trompet and {van Schoor}, N.M. and K. Zhu and B.M. Buckley and C. Cooper and I. Ford and D. Goltzman and J. Gonzalez-Macias and B.L. Langdahl and W.D. Leslie and P.T.A.M. Lips and R.S. Lorenc and J.M. Olmos and U. Pettersson-Kymmer and D.M. Reid and J.A. Riancho and P.E. Slagboom and C. Garcia-Ibarbia and T. Ingvarsson and H. Johannsdottir and R. Luben and C. Medina-Gomez and P. Arp and K. Nandakumar and S.T. Palsson and G. Sigurdsson and {van Meurs}, J.B.J. and Y.H. Zhou and A. Hofman and J.W. Jukema and H.A.P. Pols and R.L. Prince and L.A. Cupples and C.R. Marshall and D. Pinto and D. Sato and S.W. Scherer and J. Reeve and U. Thorsteinsdottir and D. Karasik and J.B. Richards and K. Stefansson and Uitterlinden, {A. G.} and S.H. Ralston and J.P.A. Ioannidis and D.P. Kiel and F. Rivadeneira and K. Estrada",

year = "2014",

doi = "https://doi.org/10.1136/jmedgenet-2013-102064",

language = "English",

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pages = "122--131",

journal = "Journal of medical genetics",

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Oei, L, Hsu, YH, Styrkarsdottir, U, Eussen, BH, Klein, A, Peters, MJ, Halldorsson, B, Liu, CT, Alonso, N, Kaptoge, SK, Thorleifsson, G, Hallmans, G, Hocking, LJ, Husted, LB, Jameson, KA, Kruk, M, Lewis, JR, Patel, MS, Scollen, S, Svensson, O, Trompet, S, van Schoor, NM, Zhu, K, Buckley, BM, Cooper, C, Ford, I, Goltzman, D, Gonzalez-Macias, J, Langdahl, BL, Leslie, WD, Lips, PTAM, Lorenc, RS, Olmos, JM, Pettersson-Kymmer, U, Reid, DM, Riancho, JA, Slagboom, PE, Garcia-Ibarbia, C, Ingvarsson, T, Johannsdottir, H, Luben, R, Medina-Gomez, C, Arp, P, Nandakumar, K, Palsson, ST, Sigurdsson, G, van Meurs, JBJ, Zhou, YH, Hofman, A, Jukema, JW, Pols, HAP, Prince, RL, Cupples, LA, Marshall, CR, Pinto, D, Sato, D, Scherer, SW, Reeve, J, Thorsteinsdottir, U, Karasik, D, Richards, JB, Stefansson, K, Uitterlinden, AG, Ralston, SH, Ioannidis, JPA, Kiel, DP, Rivadeneira, F & Estrada, K 2014, 'A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus', Journal of medical genetics, vol. 51, no. 2, pp. 122-131. https://doi.org/10.1136/jmedgenet-2013-102064

TY - JOUR

T1 - A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus

AU - Oei, L.

AU - Hsu, Y.H.

AU - Styrkarsdottir, U.

AU - Eussen, B.H.

AU - Klein, A.

AU - Peters, M.J.

AU - Halldorsson, B.

AU - Liu, C.T.

AU - Alonso, N.

AU - Kaptoge, S.K.

AU - Thorleifsson, G.

AU - Hallmans, G.

AU - Hocking, L.J.

AU - Husted, L.B.

AU - Jameson, K.A.

AU - Kruk, M.

AU - Lewis, J.R.

AU - Patel, M.S.

AU - Scollen, S.

AU - Svensson, O.

AU - Trompet, S.

AU - van Schoor, N.M.

AU - Zhu, K.

AU - Buckley, B.M.

AU - Cooper, C.

AU - Ford, I.

AU - Goltzman, D.

AU - Gonzalez-Macias, J.

AU - Langdahl, B.L.

AU - Leslie, W.D.

AU - Lips, P.T.A.M.

AU - Lorenc, R.S.

AU - Olmos, J.M.

AU - Pettersson-Kymmer, U.

AU - Reid, D.M.

AU - Riancho, J.A.

AU - Slagboom, P.E.

AU - Garcia-Ibarbia, C.

AU - Ingvarsson, T.

AU - Johannsdottir, H.

AU - Luben, R.

AU - Medina-Gomez, C.

AU - Arp, P.

AU - Nandakumar, K.

AU - Palsson, S.T.

AU - Sigurdsson, G.

AU - van Meurs, J.B.J.

AU - Zhou, Y.H.

AU - Hofman, A.

AU - Jukema, J.W.

AU - Pols, H.A.P.

AU - Prince, R.L.

AU - Cupples, L.A.

AU - Marshall, C.R.

AU - Pinto, D.

AU - Sato, D.

AU - Scherer, S.W.

AU - Reeve, J.

AU - Thorsteinsdottir, U.

AU - Karasik, D.

AU - Richards, J.B.

AU - Stefansson, K.

AU - Uitterlinden, A. G.

AU - Ralston, S.H.

AU - Ioannidis, J.P.A.

AU - Kiel, D.P.

AU - Rivadeneira, F.

AU - Estrada, K.

PY - 2014

Y1 - 2014

N2 - Background Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk. Aim To identify CNVs associated with osteoporotic bone fracture risk. Method We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies. Results A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10

AB - Background Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk. Aim To identify CNVs associated with osteoporotic bone fracture risk. Method We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies. Results A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10

U2 - https://doi.org/10.1136/jmedgenet-2013-102064

DO - https://doi.org/10.1136/jmedgenet-2013-102064

M3 - Article

C2 - 24343915

SN - 0022-2593

VL - 51

SP - 122

EP - 131

JO - Journal of medical genetics

JF - Journal of medical genetics

IS - 2

ER -