A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25.
Myopia and hyperopia are at opposite ends of the continuum of refraction, the measure of the eye's ability to focus light, which is an important cause of visual impairment (when aberrant) and is a highly heritable trait. We conducted a genome-wide association study for refractive error in 4,270 individuals from the TwinsUK cohort. We identified SNPs on 15q25 associated with refractive error (rs8027411, P = 7.91 × 10⁻⁸). We replicated this association in six adult cohorts of European ancestry with a combined 13,414 individuals (combined P = 2.07 × 10⁻⁹). This locus overlaps the transcription initiation site of RASGRF1, which is highly expressed in neurons and retina and has previously been implicated in retinal function and memory consolidation. Rasgrf1(-/-) mice show a heavier average crystalline lens (P = 0.001). The identification of a susceptibility locus for refractive error on 15q25 will be important in characterizing the molecular mechanism responsible for the most common cause of visual impairment.
Hysi
Pirro G
PG
Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, UK.
Young
Terri L
TL
Mackey
David A
DA
Andrew
Toby
T
Fernández-Medarde
Alberto
A
Solouki
Abbas M
AM
Hewitt
Alex W
AW
Macgregor
Stuart
S
Vingerling
Johannes R
JR
Li
Yi-Ju
YJ
Ikram
M Kamran
MK
Fai
Lee Yiu
LY
Sham
Pak C
PC
Manyes
Lara
L
Porteros
Angel
A
Lopes
Margarida C
MC
Carbonaro
Francis
F
Fahy
Samantha J
SJ
Martin
Nicholas G
NG
van Duijn
Cornelia M
CM
Spector
Timothy D
TD
Rahi
Jugnoo S
JS
Santos
Eugenio
E
Klaver
Caroline C W
CC
Hammond
Christopher J
CJ
D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009216:Myopia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018433:Twin Studies as Topic; D020666:ras-GRF1 / Q000235:genetics / Q000502:physiology
C513039:RASGRF1 protein, human; C513037:Rasgrf1 protein, mouse; D020666:ras-GRF1