Meta-analysis of genome-wide association studies in five cohorts reveals common variants in RBFOX1, a regulator of tissue-specific splicing, associated with refractive error.

Journal Article (Journal Article)

Visual refractive errors (REs) are complex genetic traits with a largely unknown etiology. To date, genome-wide association studies (GWASs) of moderate size have identified several novel risk markers for RE, measured here as mean spherical equivalent (MSE). We performed a GWAS using a total of 7280 samples from five cohorts: the Age-Related Eye Disease Study (AREDS); the KORA study ('Cooperative Health Research in the Region of Augsburg'); the Framingham Eye Study (FES); the Ogliastra Genetic Park-Talana (OGP-Talana) Study and the Multiethnic Study of Atherosclerosis (MESA). Genotyping was performed on Illumina and Affymetrix platforms with additional markers imputed to the HapMap II reference panel. We identified a new genome-wide significant locus on chromosome 16 (rs10500355, P = 3.9 × 10(-9)) in a combined discovery and replication set (26 953 samples). This single nucleotide polymorphism (SNP) is located within the RBFOX1 gene which is a neuron-specific splicing factor regulating a wide range of alternative splicing events implicated in neuronal development and maturation, including transcription factors, other splicing factors and synaptic proteins.

Full Text

Duke Authors

Cited Authors

  • Stambolian, D; Wojciechowski, R; Oexle, K; Pirastu, M; Li, X; Raffel, LJ; Cotch, MF; Chew, EY; Klein, B; Klein, R; Wong, TY; Simpson, CL; Klaver, CCW; van Duijn, CM; Verhoeven, VJM; Baird, PN; Vitart, V; Paterson, AD; Mitchell, P; Saw, SM; Fossarello, M; Kazmierkiewicz, K; Murgia, F; Portas, L; Schache, M; Richardson, A; Xie, J; Wang, JJ; Rochtchina, E; DCCT/EDIC Research Group, ; Viswanathan, AC; Hayward, C; Wright, AF; Polasek, O; Campbell, H; Rudan, I; Oostra, BA; Uitterlinden, AG; Hofman, A; Rivadeneira, F; Amin, N; Karssen, LC; Vingerling, JR; Hosseini, SM; Döring, A; Bettecken, T; Vatavuk, Z; Gieger, C; Wichmann, H-E; Wilson, JF; Fleck, B; Foster, PJ; Topouzis, F; McGuffin, P; Sim, X; Inouye, M; Holliday, EG; Attia, J; Scott, RJ; Rotter, JI; Meitinger, T; Bailey-Wilson, JE

Published Date

  • July 1, 2013

Published In

Volume / Issue

  • 22 / 13

Start / End Page

  • 2754 - 2764

PubMed ID

  • 23474815

Pubmed Central ID

  • PMC3674806

Electronic International Standard Serial Number (EISSN)

  • 1460-2083

Digital Object Identifier (DOI)

  • 10.1093/hmg/ddt116


  • eng

Conference Location

  • England