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

Virginie J M Verhoeven; Pirro G Hysi; Robert Wojciechowski; Qiao Fan; Jeremy A Guggenheim; René Höhn; Stuart MacGregor; Alex W Hewitt; Abhishek Nag; Ching-Yu Cheng; Ekaterina Yonova-Doing; Xin Zhou; M Kamran Ikram; Gabriëlle H S Buitendijk; George McMahon; John P Kemp; Beate St Pourcain; Claire L Simpson; Kari-Matti Mäkelä; Terho Lehtimäki; Mika Kähönen; Andrew D Paterson; S Mohsen Hosseini; Hoi Suen Wong; Liang Xu; Jost B Jonas; Olavi Pärssinen; Juho Wedenoja; Shea Ping Yip; Daniel W H Ho; Chi Pui Pang; Li Jia Chen; Kathryn P Burdon; Jamie E Craig; Barbara E K Klein; Ronald Klein; Toomas Haller; Andres Metspalu; Chiea-Chuen Khor; E-Shyong Tai; Tin Aung; Eranga Vithana; Wan-Ting Tay; Veluchamy A Barathi; Peng Chen; Ruoying Li; Jiemin Liao; Tim D Spector; Christopher J Hammond; Consortium for Refractive Error and Myopia (CREAM)

doi:10.1038/ng.2554

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

Virginie J M Verhoeven, Pirro G Hysi, Robert Wojciechowski, Qiao Fan, Jeremy A Guggenheim, René Höhn, Stuart MacGregor, Alex W Hewitt, Abhishek Nag, Ching-Yu Cheng, Ekaterina Yonova-Doing, Xin Zhou, M Kamran Ikram, Gabriëlle H S Buitendijk, George McMahon, John P Kemp, Beate St Pourcain, Claire L Simpson, Kari-Matti Mäkelä, Terho LehtimäkiMika Kähönen, Andrew D Paterson, S Mohsen Hosseini, Hoi Suen Wong, Liang Xu, Jost B Jonas, Olavi Pärssinen, Juho Wedenoja, Shea Ping Yip, Daniel W H Ho, Chi Pui Pang, Li Jia Chen, Kathryn P Burdon, Jamie E Craig, Barbara E K Klein, Ronald Klein, Toomas Haller, Andres Metspalu, Chiea-Chuen Khor, E-Shyong Tai, Tin Aung, Eranga Vithana, Wan-Ting Tay, Veluchamy A Barathi, Peng Chen, Ruoying Li, Jiemin Liao, Tim D Spector, Christopher J Hammond, Consortium for Refractive Error and Myopia (CREAM)

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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.

Original language	English
Pages (from-to)	314-318
Number of pages	5
Journal	Nature Genetics
Volume	45
Issue number	3
DOIs	https://doi.org/10.1038/ng.2554
Publication status	Published - 10 Feb 2013

Keywords

Laminin
Homeodomain Proteins
Humans
Alcohol Oxidoreductases
Bone Morphogenetic Protein 2
Myopia
Genome-Wide Association Study
Asian Continental Ancestry Group
Serine Proteases
KCNQ Potassium Channels
Risk Factors
European Continental Ancestry Group
Receptors, AMPA
Genetic Predisposition to Disease
Trans-Activators
Refractive Errors

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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. W., Nag, A., Cheng, C.-Y., 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., ... Consortium for Refractive Error and Myopia (CREAM) (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

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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.",

keywords = "Laminin, Homeodomain Proteins, Humans, Alcohol Oxidoreductases, Bone Morphogenetic Protein 2, Myopia, Genome-Wide Association Study, Asian Continental Ancestry Group, Serine Proteases, KCNQ Potassium Channels, Risk Factors, European Continental Ancestry Group, Receptors, AMPA, Genetic Predisposition to Disease, Trans-Activators, Refractive Errors",

author = "Verhoeven, {Virginie J M} and Hysi, {Pirro G} and Robert Wojciechowski and Qiao Fan and Guggenheim, {Jeremy A} and Ren{\'e} H{\"o}hn and Stuart MacGregor and Hewitt, {Alex W} and Abhishek Nag and Ching-Yu Cheng and Ekaterina Yonova-Doing and Xin Zhou and Ikram, {M Kamran} and Buitendijk, {Gabri{\"e}lle H S} and George McMahon and Kemp, {John P} and Pourcain, {Beate St} and Simpson, {Claire L} and Kari-Matti M{\"a}kel{\"a} and Terho Lehtim{\"a}ki and Mika K{\"a}h{\"o}nen and Paterson, {Andrew D} and Hosseini, {S Mohsen} and Wong, {Hoi Suen} and Liang Xu and Jonas, {Jost B} and Olavi P{\"a}rssinen and Juho Wedenoja and Yip, {Shea Ping} and Ho, {Daniel W H} and Pang, {Chi Pui} and Chen, {Li Jia} and Burdon, {Kathryn P} and Craig, {Jamie E} and Klein, {Barbara E K} and Ronald Klein and Toomas Haller and Andres Metspalu and Chiea-Chuen Khor and E-Shyong Tai and Tin Aung and Eranga Vithana and Wan-Ting Tay and Barathi, {Veluchamy A} and Peng Chen and Ruoying Li and Jiemin Liao and Spector, {Tim D} and Hammond, {Christopher J} and {Consortium for Refractive Error and Myopia (CREAM)} and Robert Plomin",

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doi = "10.1038/ng.2554",

language = "English",

volume = "45",

pages = "314--318",

journal = "Nature Genetics",

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Verhoeven, VJM, Hysi, PG, Wojciechowski, R, Fan, Q, Guggenheim, JA, Höhn, R, MacGregor, S, Hewitt, AW, Nag, A, Cheng, C-Y, Yonova-Doing, E, Zhou, X, Ikram, MK, Buitendijk, GHS, McMahon, G, Kemp, JP, Pourcain, BS, Simpson, CL, Mäkelä, K-M, Lehtimäki, T, Kähönen, M, Paterson, AD, Hosseini, SM, Wong, HS, Xu, L, Jonas, JB, Pärssinen, O, Wedenoja, J, Yip, SP, Ho, DWH, Pang, CP, Chen, LJ, Burdon, KP, Craig, JE, Klein, BEK, Klein, R, Haller, T, Metspalu, A, Khor, C-C, Tai, E-S, Aung, T, Vithana, E, Tay, W-T, Barathi, VA, Chen, P, Li, R, Liao, J, Spector, TD , Hammond, CJ & Consortium for Refractive Error and Myopia (CREAM) 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, Virginie J M

AU - Hysi, Pirro G

AU - Wojciechowski, Robert

AU - Fan, Qiao

AU - Guggenheim, Jeremy A

AU - Höhn, René

AU - MacGregor, Stuart

AU - Hewitt, Alex W

AU - Nag, Abhishek

AU - Cheng, Ching-Yu

AU - Yonova-Doing, Ekaterina

AU - Zhou, Xin

AU - Ikram, M Kamran

AU - Buitendijk, Gabriëlle H S

AU - McMahon, George

AU - Kemp, John P

AU - Pourcain, Beate St

AU - Simpson, Claire L

AU - Mäkelä, Kari-Matti

AU - Lehtimäki, Terho

AU - Kähönen, Mika

AU - Paterson, Andrew D

AU - Hosseini, S Mohsen

AU - Wong, Hoi Suen

AU - Xu, Liang

AU - Jonas, Jost B

AU - Pärssinen, Olavi

AU - Wedenoja, Juho

AU - Yip, Shea Ping

AU - Ho, Daniel W H

AU - Pang, Chi Pui

AU - Chen, Li Jia

AU - Burdon, Kathryn P

AU - Craig, Jamie E

AU - Klein, Barbara E K

AU - Klein, Ronald

AU - Haller, Toomas

AU - Metspalu, Andres

AU - Khor, Chiea-Chuen

AU - Tai, E-Shyong

AU - Aung, Tin

AU - Vithana, Eranga

AU - Tay, Wan-Ting

AU - Barathi, Veluchamy A

AU - Chen, Peng

AU - Li, Ruoying

AU - Liao, Jiemin

AU - Spector, Tim D

AU - Hammond, Christopher J

AU - Consortium for Refractive Error and Myopia (CREAM)

AU - Plomin, Robert

PY - 2013/2/10

Y1 - 2013/2/10

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.

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.

KW - Laminin

KW - Homeodomain Proteins

KW - Humans

KW - Alcohol Oxidoreductases

KW - Bone Morphogenetic Protein 2

KW - Myopia

KW - Genome-Wide Association Study

KW - Asian Continental Ancestry Group

KW - Serine Proteases

KW - KCNQ Potassium Channels

KW - Risk Factors

KW - European Continental Ancestry Group

KW - Receptors, AMPA

KW - Genetic Predisposition to Disease

KW - Trans-Activators

KW - Refractive Errors

U2 - 10.1038/ng.2554

DO - 10.1038/ng.2554

M3 - Article

C2 - 23396134

SN - 1546-1718

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

Abstract

Keywords

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