title: A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14.
abstract: Refractive errors are the most common ocular disorders worldwide and may lead to blindness. Although this trait is highly heritable, identification of susceptibility genes has been challenging. We conducted a genome-wide association study for refractive error in 5,328 individuals from a Dutch population-based study with replication in four independent cohorts (combined 10,280 individuals in the replication stage). We identified a significant association at chromosome 15q14 (rs634990, P = 2.21 × 10⁻¹⁴). The odds ratio of myopia compared to hyperopia for the minor allele (minor allele frequency = 0.47) was 1.41 (95% CI 1.16-1.70) for individuals heterozygous for the allele and 1.83 (95% CI 1.42-2.36) for individuals homozygous for the allele. The associated locus is near two genes that are expressed in the retina, GJD2 and ACTC1, and appears to harbor regulatory elements which may influence transcription of these genes. Our data suggest that common variants at 15q14 influence susceptibility for refractive errors in the general population.
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Abbas M
authors.initials: AM
authors.lastname: Solouki
authors.forename: Virginie J M
authors.initials: VJ
authors.lastname: Verhoeven
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Annemieke J M H
authors.initials: AJ
authors.lastname: Verkerk
authors.forename: M Kamran
authors.initials: MK
authors.lastname: Ikram
authors.forename: Pirro G
authors.initials: PG
authors.lastname: Hysi
authors.forename: Dominiek D G
authors.initials: DD
authors.lastname: Despriet
authors.forename: Leonieke M
authors.initials: LM
authors.lastname: van Koolwijk
authors.forename: Lintje
authors.initials: L
authors.lastname: Ho
authors.forename: Wishal D
authors.initials: WD
authors.lastname: Ramdas
authors.forename: Monika
authors.initials: M
authors.lastname: Czudowska
authors.forename: Robert W A M
authors.initials: RW
authors.lastname: Kuijpers
authors.forename: Najaf
authors.initials: N
authors.lastname: Amin
authors.forename: Maksim
authors.initials: M
authors.lastname: Struchalin
authors.forename: Yurii S
authors.initials: YS
authors.lastname: Aulchenko
authors.forename: Gabriel
authors.initials: G
authors.lastname: van Rij
authors.forename: Frans C C
authors.initials: FC
authors.lastname: Riemslag
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Theo G M F
authors.initials: TG
authors.lastname: Gorgels
authors.forename: Jacqueline J M
authors.initials: JJ
authors.lastname: Willemse-Assink
authors.forename: Aaron
authors.initials: A
authors.lastname: Isaacs
authors.forename: Rogier
authors.initials: R
authors.lastname: Kramer
authors.forename: Sigrid M A
authors.initials: SM
authors.lastname: Swagemakers
authors.forename: Arthur A B
authors.initials: AA
authors.lastname: Bergen
authors.forename: Andy A L J
authors.initials: AA
authors.lastname: van Oosterhout
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hammond
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
mesh_terms: D000199:Actins / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D017630:Connexins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009216:Myopia / Q000235:genetics*; D055815:Young Adult; D000097004:Gap Junction delta-2 Protein
chemical_list: D000199:Actins; D017630:Connexins; D000097004:Gap Junction delta-2 Protein; C526913:ACTC1 protein, human