Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium

The CREAM Consortium, Qing Li, Robert Wojciechowski, Claire L Simpson, Pirro G Hysi, Virginie J M Verhoeven, Mohammad Kamran Ikram, René Höhn, Veronique Vitart, Alex W Hewitt, Konrad Oexle, Kari-Matti Mäkelä, Stuart MacGregor, Mario Pirastu, Qiao Fan, Ching-Yu Cheng, Beaté St Pourcain, George McMahon, John P Kemp, Kate NorthstoneJugnoo S Rahi, Phillippa M Cumberland, Nicholas G Martin, Paul G Sanfilippo, Yi Lu, Ya Xing Wang, Caroline Hayward, Ozren Polašek, Harry Campbell, Goran Bencic, Alan F Wright, Juho Wedenoja, Tanja Zeller, Arne Schillert, Alireza Mirshahi, Karl Lackner, Shea Ping Yip, Maurice K H Yap, Janina S Ried, Christian Gieger, Federico Murgia, James F Wilson, Brian Fleck, Seyhan Yazar, Johannes R Vingerling, Albert Hofman, André Uitterlinden, Fernando Rivadeneira, Najaf Amin, Lennart Karssen, Ben A Oostra

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.

Original languageEnglish
Pages (from-to)131-146
Number of pages16
JournalHuman Genetics
Issue number2
Early online date4 Nov 2014
Publication statusPublished - Feb 2015


Dive into the research topics of 'Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium'. Together they form a unique fingerprint.

Cite this