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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Li, Q; Wojciechowski, R; Simpson, CL; Hysi, PG; Verhoeven, VJM; Ikram, MK; Höhn, R; Vitart, V; Hewitt, AW; Oexle, K; Mäkelä, K-M; MacGregor, S; Pirastu, M; Fan, Q; Cheng, C-Y; St Pourcain, B; McMahon, G; Kemp, JP; Northstone, K; Rahi, JS; Cumberland, PM; Martin, NG; Sanfilippo, PG; Lu, Y; Wang, YX; Hayward, C; PolaĊĦek, O; Campbell, H; Bencic, G; Wright, AF; Wedenoja, J; Zeller, T; Schillert, A; Mirshahi, A; Lackner, K; Yip, SP; Yap, MKH; Ried, JS; Gieger, C; Murgia, F; Wilson, JF; Fleck, B; Yazar, S; Vingerling, JR; Hofman, A; Uitterlinden, A; Rivadeneira, F; Amin, N; Karssen, L; Oostra, BA; Zhou, X; Teo, Y-Y; Tai, ES; Vithana, E; Barathi, V; Zheng, Y; Siantar, RG; Neelam, K; Shin, Y; Lam, J; Yonova-Doing, E; Venturini, C; Hosseini, SM; Wong, H-S; Lehtimäki, T; Kähönen, M; Raitakari, O; Timpson, NJ; Evans, DM; Khor, C-C; Aung, T; Young, TL; Mitchell, P; Klein, B; van Duijn, CM; Meitinger, T; Jonas, JB; Baird, PN; Mackey, DA; Wong, TY; Saw, S-M; Pärssinen, O; Stambolian, D; Hammond, CJ; Klaver, CCW; Williams, C; Paterson, AD; Bailey-Wilson, JE; Guggenheim, JA; CREAM Consortium,

Published Date

  • February 2015

Published In

Volume / Issue

  • 134 / 2

Start / End Page

  • 131 - 146

PubMed ID

  • 25367360

Pubmed Central ID

  • PMC4291519

Electronic International Standard Serial Number (EISSN)

  • 1432-1203

Digital Object Identifier (DOI)

  • 10.1007/s00439-014-1500-y


  • eng

Conference Location

  • Germany