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Family-based genome-wide association study of south Indian pedigrees supports WNT7B as a central corneal thickness locus

Fan, BJ; Chen, X; Sondhi, N; Sharmila, PF; Soumittra, N; Sripriya, S; Sacikala, S; ... Wiggs, JL; + view all (2018) Family-based genome-wide association study of south Indian pedigrees supports WNT7B as a central corneal thickness locus. Investigative Ophthalmology and Visual Science , 59 (6) pp. 2495-2502. 10.1167/iovs.17-23536. Green open access

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Abstract

PURPOSE: To identify genetic risk factors contributing to central corneal thickness (CCT) in individuals from South India, a population with a high prevalence of ocular disorders. METHODS: One hundred ninety-five individuals from 15 large South Indian pedigrees were genotyped using the Omni2.5 bead array. Family-based association for CCT was conducted using the score test in MERLIN. RESULTS: Genome-wide association study (GWAS) identified strongest association for single nucleotide polymorphisms (SNPs) in the first intron of WNT7B and CCT (top SNP rs9330813; β = −0.57, 95% confidence interval CI: −0.78 to −0.36; P = 1.7 × 10−7). We further investigated rs9330813 in a Latino cohort and four independent European cohorts. A meta-analysis of these data sets demonstrated statistically significant association between rs9330813 and CCT (β = −3.94, 95% CI: −5.23 to −2.66; P = 1.7 × 10−9). WNT7B SNPs located in the same genomic region that includes rs9330813 have previously been associated with CCT in Latinos but with other ocular quantitative traits related to myopia (corneal curvature and axial length) in a Japanese population (rs10453441 and rs200329677). To evaluate the specificity of the observed WNT7B association with CCT in the South Indian families, we completed an ocular phenome-wide association study (PheWAS) for the top WNT7B SNPs using 45 ocular traits measured in these same families including corneal curvature and axial length. The ocular PheWAS results indicate that in the South Indian families WNT7B SNPs are primarily associated with CCT. CONCLUSIONS: The results indicate robust evidence for association between WNT7B SNPs and CCT in South Indian pedigrees, and suggest that WNT7B SNPs can have population-specific effects on ocular quantitative traits.

Type: Article
Title: Family-based genome-wide association study of south Indian pedigrees supports WNT7B as a central corneal thickness locus
Open access status: An open access version is available from UCL Discovery
DOI: 10.1167/iovs.17-23536
Publisher version: https://doi.org/10.1167/iovs.17-23536
Language: English
Additional information: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
Keywords: Cornea central thickness, genetic association, quantitative trait, WNT7B, ocular PheWAS
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10051441
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