Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

V.J.M. Verhoeven; P.G. Hysi; R. Wojciechowski; Q. Fan; J.A. Guggenheim; R. Höhn; S. Macgregor; Alex Hewitt; A. Nag; C. Cheng; E. Yonova-Doing; X. Zhou; M.K. Ikram; G.H.S. Buitendijk; G. Mcmahon; J.P. Kemp; B.S. Pourcain; C.L. Simpson; K.M. Mäkelä; T.J. Lehtimäki; M. Kähönen; A.D. Paterson; S.M.R.S. Hosseini; H. Wong; L. Xu; J.B. Jonas; O. Pärssinen; J. Wedenoja; S. Yip; D. Ho; C. Pang; L. Chen; K.P. Burdon; J.E. Craig; B.E.K. Klein; R.E. Klein; T. Haller; A.K. Metspalu; C.C. Khor; E.S.S. Tai; T. Aung; E.N. Vithana; W. Tay; V.A. Barathi; P. Chen; R. Li; J. Liao; Y. Zheng; R. Ong; A. Döring; D.M. Evans; N.J. Timpson; A.J.M.H. Verkerk; T.A. Meitinger; O.T. Raitakari; F.A. Hawthorne; T.D. Spector; L.C. Karssen; M. Pirastu; F. Murgia; Wei Ang; A. Mishra; G.W. Montgomery; Craig Pennell; P.M. Cumberland; I. Cotlarciuc; P. Mitchell; J. Wang; M. Schäche; S. Janmahasathian; R.P. Igo; J.H. Lass; E. Chew; S.K. Iyengar; T.G.M.F. Gorgels; I. Rudan; C. Hayward; A.F. Wright; O. Polašek; Z. Vatavuk; J.F.F. Wilson; B.W. Fleck; T. Zeller; A. Mirshahi; C. Mul̈ler; A.G. Uitterlinden; F.F. Rivadeneira; J.R. Vingerling; A.F. Hofman; B.A. Oostra; N. Amin; A.A.B. Bergen; Y.Y. Teo; J.S. Rahi; V. Vitart; C.E.C.S. Williams; P.N. Baird; T. Wong; K. Oexle; N. Pfeiffer; David Mackey; T. Young; C.M.A. Van Duijn; S. Saw; J.E. Bailey-Wilson; D.E. Stambolian; C.C.W. Klaver; C.J. Hammond

doi:10.1038/ng.2554

Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

V.J.M. Verhoeven, P.G. Hysi, R. Wojciechowski, Q. Fan, J.A. Guggenheim, R. Höhn, S. Macgregor, Alex Hewitt, A. Nag, C. Cheng, E. Yonova-Doing, X. Zhou, M.K. Ikram, G.H.S. Buitendijk, G. Mcmahon, J.P. Kemp, B.S. Pourcain, C.L. Simpson, K.M. Mäkelä, T.J. LehtimäkiM. Kähönen, A.D. Paterson, S.M.R.S. Hosseini, H. Wong, L. Xu, J.B. Jonas, O. Pärssinen, J. Wedenoja, S. Yip, D. Ho, C. Pang, L. Chen, K.P. Burdon, J.E. Craig, B.E.K. Klein, R.E. Klein, T. Haller, A.K. Metspalu, C.C. Khor, E.S.S. Tai, T. Aung, E.N. Vithana, W. Tay, V.A. Barathi, P. Chen, R. Li, J. Liao, Y. Zheng, R. Ong, A. Döring, D.M. Evans, N.J. Timpson, A.J.M.H. Verkerk, T.A. Meitinger, O.T. Raitakari, F.A. Hawthorne, T.D. Spector, L.C. Karssen, M. Pirastu, F. Murgia, Wei Ang, A. Mishra, G.W. Montgomery, Craig Pennell, P.M. Cumberland, I. Cotlarciuc, P. Mitchell, J. Wang, M. Schäche, S. Janmahasathian, R.P. Igo, J.H. Lass, E. Chew, S.K. Iyengar, T.G.M.F. Gorgels, I. Rudan, C. Hayward, A.F. Wright, O. Polašek, Z. Vatavuk, J.F.F. Wilson, B.W. Fleck, T. Zeller, A. Mirshahi, C. Mul̈ler, A.G. Uitterlinden, F.F. Rivadeneira, J.R. Vingerling, A.F. Hofman, B.A. Oostra, N. Amin, A.A.B. Bergen, Y.Y. Teo, J.S. Rahi, V. Vitart, C.E.C.S. Williams, P.N. Baird, T. Wong, K. Oexle, N. Pfeiffer, David Mackey, T. Young, C.M.A. Van Duijn, S. Saw, J.E. Bailey-Wilson, D.E. Stambolian, C.C.W. Klaver, C.J. Hammond

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Abstract

Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia. © 2013 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	314-318
Journal	Nature Genetics
Volume	45
Issue number	3
DOIs	https://doi.org/10.1038/ng.2554
Publication status	Published - 2013

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10.1038/ng.2554

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Verhoeven, V. J. M., Hysi, P. G., Wojciechowski, R., Fan, Q., Guggenheim, J. A., Höhn, R., Macgregor, S., Hewitt, A., Nag, A., Cheng, C., Yonova-Doing, E., Zhou, X., Ikram, M. K., Buitendijk, G. H. S., Mcmahon, G., Kemp, J. P., Pourcain, B. S., Simpson, C. L., Mäkelä, K. M., ... Hammond, C. J. (2013). Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. Nature Genetics, 45(3), 314-318. https://doi.org/10.1038/ng.2554

@article{be31762b887d46d6b8885e4d1f91f617,

title = "Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia",

abstract = "Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia. {\textcopyright} 2013 Nature America, Inc. All rights reserved.",

author = "V.J.M. Verhoeven and P.G. Hysi and R. Wojciechowski and Q. Fan and J.A. Guggenheim and R. H{\"o}hn and S. Macgregor and Alex Hewitt and A. Nag and C. Cheng and E. Yonova-Doing and X. Zhou and M.K. Ikram and G.H.S. Buitendijk and G. Mcmahon and J.P. Kemp and B.S. Pourcain and C.L. Simpson and K.M. M{\"a}kel{\"a} and T.J. Lehtim{\"a}ki and M. K{\"a}h{\"o}nen and A.D. Paterson and S.M.R.S. Hosseini and H. Wong and L. Xu and J.B. Jonas and O. P{\"a}rssinen and J. Wedenoja and S. Yip and D. Ho and C. Pang and L. Chen and K.P. Burdon and J.E. Craig and B.E.K. Klein and R.E. Klein and T. Haller and A.K. Metspalu and C.C. Khor and E.S.S. Tai and T. Aung and E.N. Vithana and W. Tay and V.A. Barathi and P. Chen and R. Li and J. Liao and Y. Zheng and R. Ong and A. D{\"o}ring and D.M. Evans and N.J. Timpson and A.J.M.H. Verkerk and T.A. Meitinger and O.T. Raitakari and F.A. Hawthorne and T.D. Spector and L.C. Karssen and M. Pirastu and F. Murgia and Wei Ang and A. Mishra and G.W. Montgomery and Craig Pennell and P.M. Cumberland and I. Cotlarciuc and P. Mitchell and J. Wang and M. Sch{\"a}che and S. Janmahasathian and R.P. Igo and J.H. Lass and E. Chew and S.K. Iyengar and T.G.M.F. Gorgels and I. Rudan and C. Hayward and A.F. Wright and O. Pola{\v s}ek and Z. Vatavuk and J.F.F. Wilson and B.W. Fleck and T. Zeller and A. Mirshahi and C. Mu{\"l}ler and A.G. Uitterlinden and F.F. Rivadeneira and J.R. Vingerling and A.F. Hofman and B.A. Oostra and N. Amin and A.A.B. Bergen and Y.Y. Teo and J.S. Rahi and V. Vitart and C.E.C.S. Williams and P.N. Baird and T. Wong and K. Oexle and N. Pfeiffer and David Mackey and T. Young and {Van Duijn}, C.M.A. and S. Saw and J.E. Bailey-Wilson and D.E. Stambolian and C.C.W. Klaver and C.J. Hammond",

year = "2013",

doi = "10.1038/ng.2554",

language = "English",

volume = "45",

pages = "314--318",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group - Macmillan Publishers",

number = "3",

}

Verhoeven, VJM, Hysi, PG, Wojciechowski, R, Fan, Q, Guggenheim, JA, Höhn, R, Macgregor, S, Hewitt, A, Nag, A, Cheng, C, Yonova-Doing, E, Zhou, X, Ikram, MK, Buitendijk, GHS, Mcmahon, G, Kemp, JP, Pourcain, BS, Simpson, CL, Mäkelä, KM, Lehtimäki, TJ, Kähönen, M, Paterson, AD, Hosseini, SMRS, Wong, H, Xu, L, Jonas, JB, Pärssinen, O, Wedenoja, J, Yip, S, Ho, D, Pang, C, Chen, L, Burdon, KP, Craig, JE, Klein, BEK, Klein, RE, Haller, T, Metspalu, AK, Khor, CC, Tai, ESS, Aung, T, Vithana, EN, Tay, W, Barathi, VA, Chen, P, Li, R, Liao, J, Zheng, Y, Ong, R, Döring, A, Evans, DM, Timpson, NJ, Verkerk, AJMH, Meitinger, TA, Raitakari, OT, Hawthorne, FA, Spector, TD, Karssen, LC, Pirastu, M, Murgia, F, Ang, W, Mishra, A, Montgomery, GW, Pennell, C, Cumberland, PM, Cotlarciuc, I, Mitchell, P, Wang, J, Schäche, M, Janmahasathian, S, Igo, RP, Lass, JH, Chew, E, Iyengar, SK, Gorgels, TGMF, Rudan, I, Hayward, C, Wright, AF, Polašek, O, Vatavuk, Z, Wilson, JFF, Fleck, BW, Zeller, T, Mirshahi, A, Mul̈ler, C, Uitterlinden, AG, Rivadeneira, FF, Vingerling, JR, Hofman, AF, Oostra, BA, Amin, N, Bergen, AAB, Teo, YY, Rahi, JS, Vitart, V, Williams, CECS, Baird, PN, Wong, T, Oexle, K, Pfeiffer, N, Mackey, D, Young, T, Van Duijn, CMA, Saw, S, Bailey-Wilson, JE, Stambolian, DE, Klaver, CCW & Hammond, CJ 2013, 'Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia', Nature Genetics, vol. 45, no. 3, pp. 314-318. https://doi.org/10.1038/ng.2554

TY - JOUR

T1 - Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

AU - Verhoeven, V.J.M.

AU - Hysi, P.G.

AU - Wojciechowski, R.

AU - Fan, Q.

AU - Guggenheim, J.A.

AU - Höhn, R.

AU - Macgregor, S.

AU - Hewitt, Alex

AU - Nag, A.

AU - Cheng, C.

AU - Yonova-Doing, E.

AU - Zhou, X.

AU - Ikram, M.K.

AU - Buitendijk, G.H.S.

AU - Mcmahon, G.

AU - Kemp, J.P.

AU - Pourcain, B.S.

AU - Simpson, C.L.

AU - Mäkelä, K.M.

AU - Lehtimäki, T.J.

AU - Kähönen, M.

AU - Paterson, A.D.

AU - Hosseini, S.M.R.S.

AU - Wong, H.

AU - Xu, L.

AU - Jonas, J.B.

AU - Pärssinen, O.

AU - Wedenoja, J.

AU - Yip, S.

AU - Ho, D.

AU - Pang, C.

AU - Chen, L.

AU - Burdon, K.P.

AU - Craig, J.E.

AU - Klein, B.E.K.

AU - Klein, R.E.

AU - Haller, T.

AU - Metspalu, A.K.

AU - Khor, C.C.

AU - Tai, E.S.S.

AU - Aung, T.

AU - Vithana, E.N.

AU - Tay, W.

AU - Barathi, V.A.

AU - Chen, P.

AU - Li, R.

AU - Liao, J.

AU - Zheng, Y.

AU - Ong, R.

AU - Döring, A.

AU - Evans, D.M.

AU - Timpson, N.J.

AU - Verkerk, A.J.M.H.

AU - Meitinger, T.A.

AU - Raitakari, O.T.

AU - Hawthorne, F.A.

AU - Spector, T.D.

AU - Karssen, L.C.

AU - Pirastu, M.

AU - Murgia, F.

AU - Ang, Wei

AU - Mishra, A.

AU - Montgomery, G.W.

AU - Pennell, Craig

AU - Cumberland, P.M.

AU - Cotlarciuc, I.

AU - Mitchell, P.

AU - Wang, J.

AU - Schäche, M.

AU - Janmahasathian, S.

AU - Igo, R.P.

AU - Lass, J.H.

AU - Chew, E.

AU - Iyengar, S.K.

AU - Gorgels, T.G.M.F.

AU - Rudan, I.

AU - Hayward, C.

AU - Wright, A.F.

AU - Polašek, O.

AU - Vatavuk, Z.

AU - Wilson, J.F.F.

AU - Fleck, B.W.

AU - Zeller, T.

AU - Mirshahi, A.

AU - Mul̈ler, C.

AU - Uitterlinden, A.G.

AU - Rivadeneira, F.F.

AU - Vingerling, J.R.

AU - Hofman, A.F.

AU - Oostra, B.A.

AU - Amin, N.

AU - Bergen, A.A.B.

AU - Teo, Y.Y.

AU - Rahi, J.S.

AU - Vitart, V.

AU - Williams, C.E.C.S.

AU - Baird, P.N.

AU - Wong, T.

AU - Oexle, K.

AU - Pfeiffer, N.

AU - Mackey, David

AU - Young, T.

AU - Van Duijn, C.M.A.

AU - Saw, S.

AU - Bailey-Wilson, J.E.

AU - Stambolian, D.E.

AU - Klaver, C.C.W.

AU - Hammond, C.J.

PY - 2013

Y1 - 2013

N2 - Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia. © 2013 Nature America, Inc. All rights reserved.

AB - Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia. © 2013 Nature America, Inc. All rights reserved.

U2 - 10.1038/ng.2554

DO - 10.1038/ng.2554

M3 - Article

C2 - 23396134

SN - 1061-4036

VL - 45

SP - 314

EP - 318

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia

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