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


Qing, L and Wojciechowski, R and Simpson, CL and Hysi, PG and Verhoeven, VJM and Ikram, MK and Hohn, R and Vitart, V and Hewitt, AW and Oexle, K and Makela, K-M and MacGregor, S and Pirastu, M and Fan, Q and Cheng, C-Y and St Pourcain, B and McMahon, G and Kemp, JP and Northstone, K and Rahi, JS and Cumberland, PM and Martin, NG and Sanfilippo, PG and Lu, Y and Wang, YX and Hayward, C and Polasek, O and Campbell, H and Bencic, G and Wright, AF and Wedenoja, J and Zeller, T and Schillert, A and Mirshahi, A and Lackner, K and Yip, SP and Yap, MKH and Ried, JS and Gieger, C and Murgia, F and Wilson, JF and Fleck, B and Yazar, S and Vingerling, JR and Hofman, A and Uitterlinden, A and Rivadeneira, F and Amin, N and Karssen, L and Oostra, BA and Zhou, X and Teo, Y-Y and Tai, ES and Vithana, E and Barathi, V and Zheng, Y and Siantar, RG and Neelam, K and Shin, Y and Lam, J and Yonova-Doing, E and Venturini, C and Hosseini, SM and Wong, H-S and Lehtimaki, T and Kahonen, M and Raitakari, O and Timpson, NJ and Evans, DM and Khor, C-C and Aung, T and Young, TL and Mitchell, P and Klein, B and van Duijn, CM and Meitinger, T and Jonas, JB and Baird, PN and Mackey, DA and Wong, TY and Saw, S-S and Parssinen, O and Stambolian, D and Hammond, CJ and Klaver, CCW and Williams, C and Paterson, AD and Bailey-Wilson, JE and Guggenheim, JA and The CREAM Consortium, Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium, Human Genetics, 134, (2) pp. 131-146. ISSN 0340-6717 (2015) [Refereed Article]

DOI: doi:10.1007/s00439-014-1500-y


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.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:113136
Year Published:2015
Web of Science® Times Cited:18
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-12-14
Last Modified:2017-11-07

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