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; Yingfeng Zheng; Rick T Ong; Angela Döring; 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, Yingfeng Zheng, Rick T Ong, Angela Döring, Consortium for Refractive Error and Myopia (CREAM)

Research output: Contribution to journal › Article › peer-review

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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)	314-8
Number of pages	5
Journal	Nature Genetics
Volume	45
Issue number	3
DOIs	https://doi.org/10.1038/ng.2554
Publication status	Published or Issued - Mar 2013
Externally published	Yes

Keywords

Alcohol Oxidoreductases
Asian Continental Ancestry Group
Bone Morphogenetic Protein 2
European Continental Ancestry Group
Genetic Predisposition to Disease
Genome-Wide Association Study
Homeodomain Proteins
Humans
KCNQ Potassium Channels
Laminin
Myopia
Receptors, AMPA
Refractive Errors
Risk Factors
Serine Proteases
Trans-Activators
Journal Article
Meta-Analysis
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

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10.1038/ng.2554

Cite this

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), 314-8. https://doi.org/10.1038/ng.2554

@article{ab29a694fbae47feb761c967540a2999,

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 = "Alcohol Oxidoreductases, Asian Continental Ancestry Group, Bone Morphogenetic Protein 2, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Homeodomain Proteins, Humans, KCNQ Potassium Channels, Laminin, Myopia, Receptors, AMPA, Refractive Errors, Risk Factors, Serine Proteases, Trans-Activators, Journal Article, Meta-Analysis, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't",

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 Yingfeng Zheng and Ong, {Rick T} and Angela D{\"o}ring and {Consortium for Refractive Error and Myopia (CREAM)}",

year = "2013",

month = mar,

doi = "10.1038/ng.2554",

language = "English",

volume = "45",

pages = "314--8",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "3",

}

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, Zheng, Y, Ong, RT, Döring, A & 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. 314-8. 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 - Zheng, Yingfeng

AU - Ong, Rick T

AU - Döring, Angela

AU - Consortium for Refractive Error and Myopia (CREAM)

PY - 2013/3

Y1 - 2013/3

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 - Alcohol Oxidoreductases

KW - Asian Continental Ancestry Group

KW - Bone Morphogenetic Protein 2

KW - European Continental Ancestry Group

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Homeodomain Proteins

KW - Humans

KW - KCNQ Potassium Channels

KW - Laminin

KW - Myopia

KW - Receptors, AMPA

KW - Refractive Errors

KW - Risk Factors

KW - Serine Proteases

KW - Trans-Activators

KW - Journal Article

KW - Meta-Analysis

KW - Multicenter Study

KW - Research Support, N.I.H., Extramural

KW - Research Support, N.I.H., Intramural

KW - Research Support, Non-U.S. Gov't

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 -