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 language | English |
|---|---|
| Pages (from-to) | 2754-2764 |
| Number of pages | 11 |
| Journal | Human Molecular Genetics |
| Volume | 22 |
| Issue number | 13 |
| DOIs | |
| State | Published - Jul 2013 |
Fingerprint
Dive into the research topics of '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'. Together they form a unique fingerprint.Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
In: Human Molecular Genetics, Vol. 22, No. 13, 07.2013, p. 2754-2764.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
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 L.
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.
N1 - Funding Information: This work was funded in part by the Intramural Research Program of the National Human Genome Research Institute (J.E.B.W., R.W., C.L.S.) and the National Eye Institute (M.C., E.Y.C.), National Institutes of Health and NIH RO1EY020483 (D.S., J.E.B.W.) and K08EY022943 (R.W.). The KORA Study is supported by funds from Helmholtz Center Munich and the German Federal Ministry of Education and Research (BMBF). The Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SNP Health Association Resource (SHARe) are conducted and supported by the National Heart, Lung and Blood Institute (NHLBI) in collaboration with MESA investigators. Support is provided by grants and contracts N01 HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and RR-024156. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-6-4278. Funding for the collection of RE data was supported by the Intramural Research Program of the National Eye Institute (ZIAEY000403). Support was also provided by the National Center for Research Resources, Grant UL1RR033176, and is now at the National Center for Advancing Translational Sciences, Grant UL1TR000124. The Blue Mountains Eye Study was supported by the Australian National Health & Medical Research Council (NHMRC) project grants (IDs 974159, 991407, 211069 and 457349) and Centre for Clinical Research Excellence (CCRE) in Translational Clinical Research in Eye Diseases, CCRE in TCR-Eye (ID 529923). The Blue Mountains Eye Study GWAS and genotyping costs were supported by Australian NHMRC project grants (IDs 512423, 475604, 529912 and 590204), and the Wellcome Trust, UK, as part of Wellcome Trust Case Control Consortium 2 (grant IDs 085475/B/08/Z and 085475/08/Z). E.G.H. (631096), P.N.B. (1028444) and J.W. (358702 and 632909) are supported by the NHMRC fellowship scheme. The Center for Eye Research Australia receives Operational Infrastructure Support from the Victorian government. OGP-Talana was supported by grants from the Italian Ministry of Education, University and Research (MIUR) No. 5571/DSPAR/2002 and (FIRB) D.M no. 718/Ric/2005. The DCCT Research Group is sponsored through research contracts from the National Institute of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, N01-DK-6-2204, R01-DK-077510) and the National Institutes of Health. A.D.P. holds a Canada Research Chair in the Genetics of Complex Diseases. The Rotterdam Study and ERF were supported by the Netherlands Organization of Scientific Research (NWO) (Vidi 91796357); Erasmus Medical Center and Erasmus University, Rotterdam, The Netherlands; Netherlands Organization for Health Research and Development (ZonMw); UitZicht; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission (DG XII); the Municipality of Rotterdam; the Netherlands Genomics Initiative/NWO; Center for Medical Systems Biology of NGI; Lijf en Leven; M.D. Fonds; Henkes Stichting; Stichting Nederlands Oogheelkundig Onder-zoek; Swart van Essen; Bevordering van Volkskracht; Blinden-hulp; Landelijke Stichting voor Blinden en Slechtzienden; Rotterdamse Vereniging voor Blindenbelangen; OOG; Alge-mene Nederlandse Vereniging ter Voorkoming van Blindheid; the Rotterdam Eye Hospital Research Foundation and Topcon Europe. The Croatian studies were funded by grants from the Medical Research Council (UK), from the Republic of Croatia Ministry of Science, Education and Sports (108-1080315-0302). We acknowledge the Wellcome Trust Clinical facility (Edinburgh) for the genotyping of the CROATIA-Vis study, an EU framework 6 project EUROSPAN (contract no LSHG-CT-2006-018947) for the genotyping of the CROATIA-Korcula study that was performed at the Helmholtz Zentrum Munchen (Munich, Germany). ORCADES was supported by the Chief Scientist Office of the Scottish Government, the Royal Society, the Medical Research Council Human Genetics Unit and the European Union framework program 6 EURO-SPAN project (contract no. LSHG-CT-2006-018947). Funding Information: We thank numerous clinicians, clinical staff, patients and their families for their participation in and dedication to the project; the Ogliastra population and all the individuals who participated in this study. We are very grateful to the municipal administrators for their collaboration to the project and for economic and logistic support. We are extremely appreciative of the support and wisdom provided by Dr Hemin Chin of the National Eye Institute. The Center for Inherited Disease Research, fully funded through a federal contract (HHSN268200782096C) from National Institutes of Health to The Johns Hopkins University, performed genotyping of the AREDS and KORA cohorts. Clinical data and DNA from the DCCT/EDIC study will be made available through the National Institute of Diabetes and Digestive and Kidney Diseases repository at https://www.niddkrep ository.org/niddk/home.do, last accessed date on March 13, 2013. This manuscript was not prepared under the auspices of and does not represent analyses or conclusions of the NIDDK Central Repositories, or the NIH. Rotterdam Study and ERF thank Ada Hooghart, Corina Brussee, Riet Bernaerts-Biskop, Patricia van Hilten, Pascal Arp, Jeanette Vergeer, Marijn Verkerk and Sander Bervoets. We acknowledge the Wellcome Trust Clinical facility (Edinburgh) for DNA extraction for the ORCADES study and Peter Lichner and the Helmholtz Zentrum Munchen genotyping staff (Munich, Germany) for genotyping.
PY - 2013/7
Y1 - 2013/7
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84878921285&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddt116
DO - 10.1093/hmg/ddt116
M3 - Article
C2 - 23474815
AN - SCOPUS:84878921285
SN - 0964-6906
VL - 22
SP - 2754
EP - 2764
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 13
ER -