PubMed ID:
23396134
Public Release Type:
Journal
Publication Year: 2013
Affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
DOI:
https://doi.org/10.1038/ng.2554
Authors:
Lee J,
Zhou X,
Zhou X,
Zhou X,
Zhou X,
Brown M,
Herman WH,
Aiello LP,
Albers J,
Aldave A,
Alfonso E,
Amin N,
Angus E,
Ang W,
Ang W,
Arrigg P,
Aung T,
Ayres B,
Bailey-Wilson JE,
Baird PN,
Baird PN,
Baird PN,
Baker L,
Band G,
Bantle J,
Barathi VA,
Baratz K,
Bardenstein D,
Barroso I,
Bayless M,
Beaser R,
Belin MW,
Bellenguez C,
Bergen AA,
Bergenstal R,
Biino G,
Blackburn H,
Blackwell JM,
Blevins A,
Borecki I,
Bourne PA,
Bourne W,
Bowman W,
Brabham M,
Bracey M,
Bramon E,
Brandle M,
Braunstein S,
Brillon D,
Brown-Friday J,
Brown MA,
Brucker A,
Buitendijk GH,
Bumpstead SJ,
Burdon KP,
Burdon KP,
Cagliero E,
Campbell H,
Canady JL,
Carey JD,
Casas JP,
Caudill J,
Caulder S,
Cavanaugh H,
Chan R,
Chapin JE,
Cheng CY,
Cheng CY,
Chen LJ,
Chen P,
Chen P,
Chen W,
Chew E,
Chew E,
Chin H,
Chodosh J,
Cochrane A,
Cohen E,
Colby K,
Colwell J,
Comer G,
Consortium for Refractive Error and Myopia (CREAM),
Corvin A,
Cotlarciuc I,
Counts D,
Craig JE,
Craig JE,
Crandall J,
Croasdale C,
Crofford O,
Crowell S,
Cumberland PM,
Dahms W,
Davey-Smith G,
Davis EA,
Deangelis MM,
Delcourt C,
Deloukas P,
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Group,
Djalilian A,
Donnelly P,
Donner T,
Döring A,
Dronov S,
Duncanson A,
Dunn SP,
Dupps B,
Edkins S,
Elner S,
Elsing S,
Engel H,
Engel S,
Etzwiler D,
Evans DM,
Fahmy A,
Fan Q,
Fan Q,
Farr A,
Feldman E,
Feng S,
Fernandes J,
Fleck B,
Fleck B,
Fogarty RD,
Folino K,
Fondran JR,
Freeman C,
Fritz S,
Fuchs' Genetics Multi-Center Study Group,
Galentine PG,
Galprin A,
Ganda O,
Gardner T,
Gauthier-Kelly C,
Genuth S,
Genuth S,
Giangiacomo J,
Giannoulatou E,
Gill M,
Gillman M,
Goddard K,
Godine J,
Goings L,
Goldbaum M,
Golden E,
Goldstein D,
Gordon J,
Gorgels TG,
Gorovoy M,
Gothrup J,
Gray E,
Greene DA,
Gubitosi-Klug R,
Guggenheim JA,
Guggenheim JA,
Gwilliam R,
Hackel R,
Hainsworth D,
Haller T,
Haller T,
Hamdy O,
Hamilton S,
Hammersmith K,
Hammond CJ,
Hammond CJ,
Hammond N,
Hansen K,
Hardten DR,
Hauswirth S,
Hawthorne F,
Hayward C,
Hayward C,
Hebdon M,
Heidemann DG,
Heinemann M,
Hellenthal G,
Hemady R,
Hermayer K,
Hewitt AW,
Hewitt AW,
Hitt S,
Ho DW,
Ho DW,
Hofman A,
Höhn R,
Höhn R,
Holland G,
Hosseini S,
Hosseini S,
Hosseini SM,
Hunt SE,
Hwang D,
Hysi PG,
Hysi PG,
Hysi PG,
Igo RP Jr,
Igo RP Jr,
Ikram M,
Ikram MK,
Iyengar SK,
Iyengar SK,
Iyengar SK,
Iyengar SK,
Iyengar SK,
Jacobson A,
Jampol L,
Jankowski J,
Janmahasathian S,
Janmahasatian S,
Jayakumar A,
Johnsonbaugh S,
Johnson M,
Jonas JB,
Jonas JB,
Jonas JB,
Jones B,
Jones J,
Jurkunas U,
Kähönen M,
Kähönen M,
Kaminski L,
Karp C,
Karssen LC,
Kelly K,
Kemp JP,
Ketai C LH,
Khor CC,
Kim K,
Kiss S,
Klaver CC,
Klaver CC,
Klaver CC,
Klein BE,
Klein R,
Kolterman O,
Kowarski A,
Kruger D,
Kwon S,
Lackaye ME,
Laibson P,
Langford C,
Larkin M,
Lass J,
Lass JH,
Lee D,
Lee K,
Lee T,
Lee W,
Lee Y,
Lehtimäki T,
Lehtimäki T,
Liao J,
Liddle J,
Lindsey P,
Lindstrom R,
Li R,
Liss R,
Lopes-Virella M,
Lorenzi G,
Lou P,
Luttrell L,
Lu Y,
Lyon A,
Lyons T,
MacGregor S,
MacGregor S,
MacGregor S,
Mackey DA,
Mackey M,
Maguire L,
Mäkelä KM,
Mäkelä KM,
Mannis M,
Markus HS,
Martin CL,
Martinez H,
Maschak-Carey BJ,
Mathew CG,
Maubaret C,
Mayer L,
Mayfield R,
McCann OT,
McCulley J,
McLellan M,
McMahon G,
Meguro A,
Meisler DM,
Meitinger T,
Meitinger T,
Metspalu A,
Metspalu A,
Mian S,
Mifflin M,
Mihailov E,
Miller D,
Mirshahi A,
Mirza R,
Mishra A,
Mitchell P,
Mitchell P,
Miyake M,
Miyak M,
Mizuki N,
Molitch M,
Mondino BJ,
Montgomery GW,
Mootha V,
Morason T,
Morgan K,
Morrison M,
Müller C,
Murgia F,
Murgia F,
Nag A,
Nangia V,
Nathan DM,
Nathan DM,
Northstone K,
Novak M,
Nutaitis M,
Oexle K,
Oexle K,
Oliva M,
Olsen T,
Olson R,
Ong M,
Ong RT,
Oostra BA,
Ostrowski D,
Palmer CN,
Palmert M,
Pang CP,
Pang CP,
Parker J,
Pärssinen O,
Pärssinen O,
Pärssinen O,
Patel N,
Patel S,
Paterson AD,
Paterson AD,
Paterson AD,
Pearson R,
Pendegast S,
Pennell CE,
Peters F,
Pfeiffer N,
Pfeiffer N,
Phillips M,
Pirastu M,
Pirastu M,
Pirinen M,
Pittman C,
Plomin R,
Polasek O,
Polasek O,
Pop-Busui R,
Portas L,
Potter SC,
Pourcain BS,
Price F,
Price M,
Prosser L,
Prusak R,
Quin J,
Rahi JS,
Rahi JS,
Raitakari O,
Raitakari O,
Rand L,
Rapuano C,
Rath P,
Rautanen A,
Ravindrarajah R,
Reeves S,
Reid M,
Reinhart W,
Renucci A,
Reppucci V,
Ricketts M,
Ring SM,
Rivadeneira F,
Rochtchina E,
Rogness B,
Rosenfeld SI,
Rosenwasser G,
Rosenzwieg J,
Rotkis W,
Rudan I,
Rudan I,
Ryan D,
Salemi P,
Sarma A,
Sawcer SJ,
Saw SM,
Saw SM,
Schache M,
Schache M,
Schade DS,
Schaefer B,
Schlossman D,
Schultze RL,
Schwartz S,
Selby J,
Service J,
Shamie N,
Shamoon H,
Sharuk G,
Shaughnessy M,
Sheindlin J,
Simjanoski E,
Simpson CL,
Singerman L,
Sivitz W,
Smith A,
Smith-Brewer S,
Soong KH,
Soule J,
Spector TD,
Spencer CC,
Spencer M,
Stambolian D,
Stambolian D,
Stambolian D,
Steidl S,
Steinemann T,
Steuer E,
Stevens MJ,
Stone D,
Strange A,
Strugula Z,
Suedekum B,
Sugar A,
Sugar J,
Su Z,
Szpiech M,
Tai ES,
Tay WT,
Teo YY,
Teo YY,
Terry M,
Thomas A,
Thompson T,
Timpson NJ,
Titus P,
Trembath RC,
Tu E,
Uitterlinden AG,
van Duijn CM,
van Duijn CM,
van Duijn CM,
Varma R,
Vatavuk Z,
Vatavuk Z,
Verdier D,
Verhoeven VJ,
Verhoeven VJ,
Verhoeven VJ,
Verity S,
Verkerk AJ,
Vine AK,
Vingerling JR,
Viswanathan AC,
Vital M,
Vitart V,
Vitart V,
Vitart V,
Vitart V,
Vitart V,
Vithana E,
Vukcevic D,
Waller M,
Wang JJ,
Wang JJ,
Wedenoja J,
Wegner A,
Wellcome Trust Case Control Consortium 2 (WTCCC2),
Weston P,
Whitehouse F,
Whittaker P,
Widaa S,
Williams C,
Williams C,
Wilson JE,
Wilson JE,
Wilson JF,
Wilson JF,
Wilson JW,
Wimmergren N,
Wojciechowski R,
Wojciechowski R,
Wolpert H,
Wong HS,
Wong TY,
Wong TY,
Wood D,
Wood NW,
Wright AF,
Wright AF,
Xu L,
Xu L,
Yacoub-Wasef S,
Yamashiro K,
Yamashiro K,
Yee R,
Yip SP,
Yip SP,
Yonova-Doing E,
Yoo S,
Yoshimura N,
Yoshimura N,
Young TL,
Young TL,
Zegarra H,
Zeller T,
Zheng Y,
Ziegler G,
Zinman B
Studies:
Diabetes Control and Complications Trial
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.