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

DCCT/EDIC Research Group, Dwight Stambolian, Robert Wojciechowski, Konrad Oexle, Mario Pirastu, Xiaohui Li, Leslie J Raffel, Mary Frances Cotch, Emily Y Chew, Barbara Klein, Ronald Klein, Tien Y Wong, Claire L Simpson, Caroline C W Klaver, Cornelia M van Duijn, Virginie J M Verhoeven, Paul N Baird, Veronique Vitart, Andrew D Paterson, Paul MitchellSeang Mei Saw, Maurizio Fossarello, Krista Kazmierkiewicz, Federico Murgia, Laura Portas, Maria Schache, Andrea Richardson, Jing Xie, Jie Jin Wang, Elena Rochtchina, Ananth C Viswanathan, Caroline Hayward, Alan F Wright, Ozren Polasek, Harry Campbell, Igor Rudan, Ben A Oostra, André G Uitterlinden, Albert Hofman, Fernando Rivadeneira, Najaf Amin, Lennart C Karssen, Johannes R Vingerling, S M Hosseini, Angela Döring, Thomas Bettecken, Zoran Vatavuk, Christian Gieger, H-Erich Wichmann, James F Wilson, Brian Fleck

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)2754-2764
Number of pages11
JournalHuman Molecular Genetics
Volume22
Issue number13
Early online date27 Mar 2013
DOIs
Publication statusPublished - 1 Jul 2013

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