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

Dwight Stambolian, Robert Wojciechowski, Konrad Oexle, Mario Pirastu, Xiaohui Li, Leslie J. Raffe, Mary Frances Cotch, Emily Y. Chew, Barbara Klein, Ronald Klein, Tien Y. Wong, Claire Simpson, Caroline C.W. Klaver, Cornelia M. van Duijn, Virginie J.M. Verhoeven, Paul N. Baird, Veronique Vitart, Andrew D. Paterson, Paul Mitchell, Seang Mei Saw & 41 others 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 Polašek, 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, Paul J. Foster, Fotis Topouzis, Peter McGuffin, Xueling Sim, Michael Inouye, Elizabeth G. Holliday, John Attia, Rodney J. Scott, Jerome I. Rotter, Thomas Meitinger, Joan E. Bailey-Wilson

Research output: Contribution to journalArticle

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Abstract

Visual refractive errors (REs) are complex genetic traits with a largely unknown etiology. To date, genomewide 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 (OGPTalana) 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 (US)
Pages (from-to)2754-2764
Number of pages11
JournalHuman molecular genetics
Volume22
Issue number13
DOIs
StatePublished - Jul 1 2013

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Refractive Errors
Genome-Wide Association Study
Meta-Analysis
HapMap Project
Chromosomes, Human, Pair 16
Eye Diseases
Alternative Splicing
Single Nucleotide Polymorphism
Atherosclerosis
Transcription Factors
Genome
Neurons
Health
Research
Genes
Proteins
RNA Splicing Factors

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

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. / Stambolian, Dwight; Wojciechowski, Robert; Oexle, Konrad; Pirastu, Mario; Li, Xiaohui; Raffe, Leslie J.; Cotch, Mary Frances; Chew, Emily Y.; Klein, Barbara; Klein, Ronald; Wong, Tien Y.; Simpson, Claire; Klaver, Caroline C.W.; van Duijn, Cornelia M.; Verhoeven, Virginie J.M.; 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, S. M.; 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.

In: Human molecular genetics, Vol. 22, No. 13, 01.07.2013, p. 2754-2764.

Research output: Contribution to journalArticle

Stambolian, D, Wojciechowski, R, Oexle, K, Pirastu, M, Li, X, Raffe, LJ, Cotch, MF, Chew, EY, Klein, B, Klein, R, Wong, TY, Simpson, C, 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, Viswanathan, AC, Hayward, C, Wright, AF, Polašek, 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, HE, 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 2013, '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', Human molecular genetics, vol. 22, no. 13, pp. 2754-2764. https://doi.org/10.1093/hmg/ddt116
Stambolian, Dwight ; Wojciechowski, Robert ; Oexle, Konrad ; Pirastu, Mario ; Li, Xiaohui ; Raffe, Leslie J. ; Cotch, Mary Frances ; Chew, Emily Y. ; Klein, Barbara ; Klein, Ronald ; Wong, Tien Y. ; Simpson, Claire ; Klaver, Caroline C.W. ; van Duijn, Cornelia M. ; Verhoeven, Virginie J.M. ; 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, S. M. ; 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. / 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. In: Human molecular genetics. 2013 ; Vol. 22, No. 13. pp. 2754-2764.
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abstract = "Visual refractive errors (REs) are complex genetic traits with a largely unknown etiology. To date, genomewide 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 (OGPTalana) 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.",
author = "Dwight Stambolian and Robert Wojciechowski and Konrad Oexle and Mario Pirastu and Xiaohui Li and Raffe, {Leslie J.} and Cotch, {Mary Frances} and Chew, {Emily Y.} and Barbara Klein and Ronald Klein and Wong, {Tien Y.} and Claire Simpson and Klaver, {Caroline C.W.} and {van Duijn}, {Cornelia M.} and Verhoeven, {Virginie J.M.} and Baird, {Paul N.} and Veronique Vitart and Paterson, {Andrew D.} and Paul Mitchell and Saw, {Seang Mei} and Maurizio Fossarello and Krista Kazmierkiewicz and Federico Murgia and Laura Portas and Maria Schache and Andrea Richardson and Jing Xie and Wang, {Jie Jin} and Elena Rochtchina and Viswanathan, {Ananth C.} and Caroline Hayward and Wright, {Alan F.} and Ozren Polašek and Harry Campbell and Igor Rudan and Oostra, {Ben A.} and Uitterlinden, {Andr{\'e} G.} and Albert Hofman and Fernando Rivadeneira and Najaf Amin and Karssen, {Lennart C.} and Vingerling, {Johannes R.} and Hosseini, {S. M.} and Angela D{\"o}ring and Thomas Bettecken and Zoran Vatavuk and Christian Gieger and Wichmann, {H. Erich} and Wilson, {James F.} and Brian Fleck and Foster, {Paul J.} and Fotis Topouzis and Peter McGuffin and Xueling Sim and Michael Inouye and Holliday, {Elizabeth G.} and John Attia and Scott, {Rodney J.} and Rotter, {Jerome I.} and Thomas Meitinger and Bailey-Wilson, {Joan E.}",
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T1 - 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

AU - Stambolian, Dwight

AU - Wojciechowski, Robert

AU - Oexle, Konrad

AU - Pirastu, Mario

AU - Li, Xiaohui

AU - Raffe, Leslie J.

AU - Cotch, Mary Frances

AU - Chew, Emily Y.

AU - Klein, Barbara

AU - Klein, Ronald

AU - Wong, Tien Y.

AU - Simpson, Claire

AU - Klaver, Caroline C.W.

AU - van Duijn, Cornelia M.

AU - Verhoeven, Virginie J.M.

AU - Baird, Paul N.

AU - Vitart, Veronique

AU - Paterson, Andrew D.

AU - Mitchell, Paul

AU - Saw, Seang Mei

AU - Fossarello, Maurizio

AU - Kazmierkiewicz, Krista

AU - Murgia, Federico

AU - Portas, Laura

AU - Schache, Maria

AU - Richardson, Andrea

AU - Xie, Jing

AU - Wang, Jie Jin

AU - Rochtchina, Elena

AU - Viswanathan, Ananth C.

AU - Hayward, Caroline

AU - Wright, Alan F.

AU - Polašek, Ozren

AU - Campbell, Harry

AU - Rudan, Igor

AU - Oostra, Ben A.

AU - Uitterlinden, André G.

AU - Hofman, Albert

AU - Rivadeneira, Fernando

AU - Amin, Najaf

AU - Karssen, Lennart C.

AU - Vingerling, Johannes R.

AU - Hosseini, S. M.

AU - Döring, Angela

AU - Bettecken, Thomas

AU - Vatavuk, Zoran

AU - Gieger, Christian

AU - Wichmann, H. Erich

AU - Wilson, James F.

AU - Fleck, Brian

AU - Foster, Paul J.

AU - Topouzis, Fotis

AU - McGuffin, Peter

AU - Sim, Xueling

AU - Inouye, Michael

AU - Holliday, Elizabeth G.

AU - Attia, John

AU - Scott, Rodney J.

AU - Rotter, Jerome I.

AU - Meitinger, Thomas

AU - Bailey-Wilson, Joan E.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - Visual refractive errors (REs) are complex genetic traits with a largely unknown etiology. To date, genomewide 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 (OGPTalana) 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.

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U2 - 10.1093/hmg/ddt116

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