Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: 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 Northstone, Jugnoo S Rahi & 31 others 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, CREAM Consortium

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14 Citations (Scopus)


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.

Number of pages16
JournalHuman Genetics
Issue number2
Publication statusPublished - Feb 2015
Externally publishedYes


  • Adult
  • Age Factors
  • Asian Continental Ancestry Group
  • Astigmatism
  • Cell Adhesion Molecules, Neuronal
  • Cohort Studies
  • European Continental Ancestry Group
  • Female
  • Genetic Markers
  • Genome-Wide Association Study
  • High Mobility Group Proteins
  • Humans
  • Male
  • Middle Aged
  • Nerve Tissue Proteins
  • Journal Article
  • Meta-Analysis

Cite this

Li, Q., Wojciechowski, R., Simpson, C. L., Hysi, P. G., Verhoeven, V. J. M., Ikram, M. K., ... CREAM Consortium (2015). Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium. Human Genetics, 134(2), 131-46.