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

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 - Evans, David M

AU - Timpson, Nicholas J

AU - Verkerk, Annemieke J M H

AU - Meitinger, Thomas

AU - Raitakari, Olli

AU - Hawthorne, Felicia

AU - Spector, Tim D

AU - Karssen, Lennart C

AU - Pirastu, Mario

AU - Murgia, Federico

AU - Ang, Wei

AU - Mishra, Aniket

AU - Montgomery, Grant W

AU - Pennell, Craig E

AU - Cumberland, Phillippa M

AU - Cotlarciuc, Ioana

AU - Mitchell, Paul

AU - Wang, Jie Jin

AU - Schache, Maria

AU - Janmahasatian, Sarayut

AU - Janmahasathian, Sarayut

AU - Igo, Robert P

AU - Lass, Jonathan H

AU - Chew, Emily

AU - Iyengar, Sudha K

AU - Gorgels, Theo G M F

AU - Rudan, Igor

AU - Hayward, Caroline

AU - Wright, Alan F

AU - Polasek, Ozren

AU - Vatavuk, Zoran

AU - Wilson, James F

AU - Fleck, Brian

AU - Zeller, Tanja

AU - Mirshahi, Alireza

AU - Müller, Christian

AU - Uitterlinden, André G

AU - Rivadeneira, Fernando

AU - Vingerling, Johannes R

AU - Hofman, Albert

AU - Oostra, Ben A

AU - Amin, Najaf

AU - Bergen, Arthur A B

AU - Teo, Yik-Ying

AU - Rahi, Jugnoo S

AU - Vitart, Veronique

AU - Williams, Cathy

AU - Baird, Paul N

AU - Wong, Tien-Yin

AU - Oexle, Konrad

AU - Pfeiffer, Norbert

AU - Mackey, David A

AU - Young, Terri L

AU - van Duijn, Cornelia M

AU - Saw, Seang-Mei

AU - Bailey-Wilson, Joan E

AU - Stambolian, Dwight

AU - Klaver, Caroline C

AU - Hammond, Christopher J

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/genetics

KW - Asian Continental Ancestry Group/genetics

KW - Bone Morphogenetic Protein 2/genetics

KW - European Continental Ancestry Group/genetics

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Homeodomain Proteins/genetics

KW - Humans

KW - KCNQ Potassium Channels/genetics

KW - Laminin/genetics

KW - Myopia/genetics

KW - Receptors, AMPA/genetics

KW - Refractive Errors/genetics

KW - Risk Factors

KW - Serine Proteases/genetics

KW - Trans-Activators/genetics

U2 - 10.1038/ng.2554

DO - 10.1038/ng.2554

M3 - SCORING: Journal article

C2 - 23396134

VL - 45

SP - 314

EP - 318

JO - NAT GENET

JF - NAT GENET

SN - 1061-4036

IS - 3

ER -