A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14.
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.
Solouki
Abbas M
AM
Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
Verhoeven
Virginie J M
VJ
van Duijn
Cornelia M
CM
Verkerk
Annemieke J M H
AJ
Ikram
M Kamran
MK
Hysi
Pirro G
PG
Despriet
Dominiek D G
DD
van Koolwijk
Leonieke M
LM
Ho
Lintje
L
Ramdas
Wishal D
WD
Czudowska
Monika
M
Kuijpers
Robert W A M
RW
Amin
Najaf
N
Struchalin
Maksim
M
Aulchenko
Yurii S
YS
van Rij
Gabriel
G
Riemslag
Frans C C
FC
Young
Terri L
TL
Mackey
David A
DA
Spector
Timothy D
TD
Gorgels
Theo G M F
TG
Willemse-Assink
Jacqueline J M
JJ
Isaacs
Aaron
A
Kramer
Rogier
R
Swagemakers
Sigrid M A
SM
Bergen
Arthur A B
AA
van Oosterhout
Andy A L J
AA
Oostra
Ben A
BA
Rivadeneira
Fernando
F
Uitterlinden
André G
AG
Hofman
Albert
A
de Jong
Paulus T V M
PT
Hammond
Christopher J
CJ
Vingerling
Johannes R
JR
Klaver
Caroline C W
CC
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
D000199:Actins; D017630:Connexins; D000097004:Gap Junction delta-2 Protein; C526913:ACTC1 protein, human