title: A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25.
abstract: 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.
authors.affiliation: Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, UK.
authors.forename: Pirro G
authors.initials: PG
authors.lastname: Hysi
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Toby
authors.initials: T
authors.lastname: Andrew
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernández-Medarde
authors.forename: Abbas M
authors.initials: AM
authors.lastname: Solouki
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.forename: Stuart
authors.initials: S
authors.lastname: Macgregor
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
authors.forename: M Kamran
authors.initials: MK
authors.lastname: Ikram
authors.forename: Lee Yiu
authors.initials: LY
authors.lastname: Fai
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
authors.forename: Lara
authors.initials: L
authors.lastname: Manyes
authors.forename: Angel
authors.initials: A
authors.lastname: Porteros
authors.forename: Margarida C
authors.initials: MC
authors.lastname: Lopes
authors.forename: Francis
authors.initials: F
authors.lastname: Carbonaro
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Fahy
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Jugnoo S
authors.initials: JS
authors.lastname: Rahi
authors.forename: Eugenio
authors.initials: E
authors.lastname: Santos
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hammond
mesh_terms: 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
chemical_list: C513039:RASGRF1 protein, human; C513037:Rasgrf1 protein, mouse; D020666:ras-GRF1