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 Academic Article uri icon

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.

authors

  • Stambolian, Dwight
  • Wojciechowski, Robert
  • Oexle, Konrad
  • Pirastu, Mario
  • Li, Xiaohui
  • Raffel, Leslie J
  • Cotch, Mary Frances
  • Chew, Emily Y
  • Klein, Barbara
  • Klein, Ronald
  • Wong, Tien Y
  • Simpson, Claire L
  • Klaver, Caroline CW
  • van Duijn, Cornelia M
  • Verhoeven, Virginie JM
  • Baird, Paul N
  • Vitart, Veronique
  • Paterson, Andrew D
  • Mitchell, Paul
  • Saw, Seang Mei
  • Fossarello, Maurizio
  • Kazmierkiewicz, Krista
  • Murgia, Federico
  • Portas, Laura
  • Schache, Maria
  • Richardson, Andrea
  • Xie, Jing
  • Wang, Jie Jin
  • Rochtchina, Elena
  • Viswanathan, Ananth C
  • Hayward, Caroline
  • Wright, Alan F
  • Polašek, Ozren
  • Campbell, Harry
  • Rudan, Igor
  • Oostra, Ben A
  • Uitterlinden, André G
  • Hofman, Albert
  • Rivadeneira, Fernando
  • Amin, Najaf
  • Karssen, Lennart C
  • Vingerling, Johannes R
  • Hosseini, SM
  • Döring, Angela
  • Bettecken, Thomas
  • Vatavuk, Zoran
  • Gieger, Christian
  • Wichmann, H-Erich
  • Wilson, James F
  • Fleck, Brian
  • Foster, Paul J
  • Topouzis, Fotis
  • McGuffin, Peter
  • Sim, Xueling
  • Inouye, Michael
  • Holliday, Elizabeth G
  • Attia, John
  • Scott, Rodney J
  • Rotter, Jerome I
  • Meitinger, Thomas
  • Bailey-Wilson, Joan E

publication date

  • 2013