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. RahiPhillippa 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, Keng Hung Maurice 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, Xin Zhou, Yik Ying Teo, E. Shyong Tai, Eranga Vithana, Veluchamy Barathi, Yingfeng Zheng, Rosalynn Grace Siantar, Kumari Neelam, Youchan Shin, Janice Lam, Ekaterina Yonova-Doing, Cristina Venturini, S. Mohsen Hosseini, Hoi Suen Wong, Terho Lehtimäki, Mika Kähönen, Olli Raitakari

Research output: Journal article publicationJournal articleAcademic researchpeer-review

19 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.
Original languageEnglish
Pages (from-to)131-146
Number of pages16
JournalHuman Genetics
Issue number2
Publication statusPublished - 13 Jan 2015

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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