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.
Title | 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. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Stambolian, D., Wojciechowski R., Oexle K., Pirastu M., Li X., Raffel L. J., Cotch M. Frances, Chew E. Y., Klein B., Klein R., Wong T. Y., Simpson C. L., Klaver C. C. W., van Duijn C. M., Verhoeven V. J. M., Baird P. N., Vitart V., Paterson A. D., Mitchell P., Saw S. Mei, Fossarello M., Kazmierkiewicz K., Murgia F., Portas L., Schache M., Richardson A., Xie J., Wang J. Jin, Rochtchina E., Viswanathan A. C., Hayward C., Wright A. F., Polasek O., Campbell H., Rudan I., Oostra B. A., Uitterlinden A. G., Hofman A., Rivadeneira F., Amin N., Karssen L. C., Vingerling J. R., Hosseini S. M., Döring A., Bettecken T., Vatavuk Z., Gieger C., Wichmann H-E., Wilson J. F., Fleck B., Foster P. J., Topouzis F., McGuffin P., Sim X., Inouye M., Holliday E. G., Attia J., Scott R. J., Rotter J. I., Meitinger T., & Bailey-Wilson J. E. |
Corporate Authors | DCCT/EDIC Research Group |
Journal | Hum Mol Genet |
Volume | 22 |
Issue | 13 |
Pagination | 2754-64 |
Date Published | 2013 Jul 1 |
ISSN | 1460-2083 |
Keywords | Adolescent, Adult, Aged, Aged, 80 and over, Cohort Studies, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Organ Specificity, Polymorphism, Single Nucleotide, Refractive Errors, RNA Isoforms, RNA Splicing, RNA-Binding Proteins, Young Adult |
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. |
DOI | 10.1093/hmg/ddt116 |
Alternate Journal | Hum. Mol. Genet. |
PubMed ID | 23474815 |
PubMed Central ID | PMC3674806 |
Grant List | 085475/08/Z / / Wellcome Trust / United Kingdom 085475/B/08/Z / / Wellcome Trust / United Kingdom CZB/4/438 / / Chief Scientist Office / United Kingdom CZB/4/710 / / Chief Scientist Office / United Kingdom K08 EY022943 / EY / NEI NIH HHS / United States K08EY022943 / EY / NEI NIH HHS / United States MC_PC_U127561128 / / Medical Research Council / United Kingdom MC_U127584475 / / Medical Research Council / United Kingdom N01 HC-95159 / HC / NHLBI NIH HHS / United States N01 HC-95160 / HC / NHLBI NIH HHS / United States N01 HC-95161 / HC / NHLBI NIH HHS / United States N01 HC-95162 / HC / NHLBI NIH HHS / United States N01 HC-95163 / HC / NHLBI NIH HHS / United States N01 HC-95164 / HC / NHLBI NIH HHS / United States N01 HC-95165 / HC / NHLBI NIH HHS / United States N01 HC-95166 / HC / NHLBI NIH HHS / United States N01 HC-95167 / HC / NHLBI NIH HHS / United States N01 HC-95168 / HC / NHLBI NIH HHS / United States N01 HC-95169 / HC / NHLBI NIH HHS / United States N01-DK-6-2204 / DK / NIDDK NIH HHS / United States N02-HL-64278 / HL / NHLBI NIH HHS / United States R01 EY016379 / EY / NEI NIH HHS / United States R01 EY020483 / EY / NEI NIH HHS / United States R01-DK-077510 / DK / NIDDK NIH HHS / United States R01EY020483 / EY / NEI NIH HHS / United States RR-024156 / RR / NCRR NIH HHS / United States UL1 TR000041 / TR / NCATS NIH HHS / United States UL1RR033176 / RR / NCRR NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States Z01 EY000403-06 / / Intramural NIH HHS / United States Z01 EY000403-07 / / Intramural NIH HHS / United States Z99 EY999999 / / Intramural NIH HHS / United States ZIA EY000403-08 / / Intramural NIH HHS / United States ZIA EY000403-09 / / Intramural NIH HHS / United States ZIA EY000403-10 / / Intramural NIH HHS / United States ZIA EY000403-11 / / Intramural NIH HHS / United States ZIAEY000403 / / PHS HHS / United States / / Chief Scientist Office / United Kingdom / / Medical Research Council / United Kingdom |