Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium
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.
基金:
NATIONAL EYE INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Eye Institute (NEI) [R01EY014685, K08EY022943, P30EY001583, R01EY024233] Funding Source: NIH RePORTER; NATIONAL HUMAN GENOME RESEARCH INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI) [ZIAHG200327] Funding Source: NIH RePORTER; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [G0400546B] Funding Source: researchfish; National Institute for Health ResearchNational Institute for Health Research (NIHR) [SRF/01/010] Funding Source: researchfish; Fight for Sight [1329/30] Funding Source: researchfish; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MC_UU_12013/4, MC_PC_U127561128, MC_UU_12013/3, G0400546] Funding Source: UKRI; Department of HealthEuropean Commission [CDF-2009-02-35, SRF/01/010] Funding Source: Medline; Medical Research CouncilUK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission [MC_PC_U127561128, MC_UU_12013/3, G0400546, MC_PC_15018, MC_UU_12013/4] Funding Source: Medline; NEI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Eye Institute (NEI) [R01 EY024233, K08 EY022943, P30 EY001583, R01 EY014685] Funding Source: Medline; Wellcome TrustWellcome TrustEuropean Commission [102215] Funding Source: Medline; Chief Scientist Office [CZB/4/710, CZB/4/438] Funding Source: Medline
Li Qing,Wojciechowski Robert,Simpson Claire L.,et al.Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium[J].HUMAN GENETICS.2015,134(2):131-146.doi:10.1007/s00439-014-1500-y.
APA:
Li, Qing,Wojciechowski, Robert,Simpson, Claire L.,Hysi, Pirro G.,Verhoeven, Virginie J. M....&Guggenheim, Jeremy A..(2015).Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium.HUMAN GENETICS,134,(2)
MLA:
Li, Qing,et al."Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium".HUMAN GENETICS 134..2(2015):131-146