Family-Based Genome-Wide Association Study of South Indian Pedigrees SupportsWNT7Bas a Central Corneal Thickness Locus

Autor: Jim Gauderman, Veronique Vitart, Jonathan L. Haines, S.E. Moroi, Srinivasan Sacikala, René Höhn, Angela J. Cree, Xueli Chen, Terri L. Young, Francesca Pasutto, Robert N. Weinreb, Joel S. Schuman, William K. Scott, Jae H. Kang, Pirro G. Hysi, Richard K. Lee, Tin Aung, Kuldev Singh, Anthony P Khawaja, Michael A. Hauser, Henriette Springelkamp, David S. Friedman, Anthony Realini, Rashima Asokan, Donald J. Zack, D. L. Budenz, Gadi Wollstein, Unnur Thorsteinsdottir, Robert P. Igo, Lingam Vijaya, Caroline C W Klaver, Jessica N. Cooke Bailey, Kathryn P. Burdon, Tien Wong, Paul Mitchell, Jerome I. Rotter, Robert Wojciechowski, Julia R. Richards, Terry Gaasterland, Douglas Vollrath, Adriana I. Iglesias Gonzalez, David A. Mackey, Puya Gharahkhani, X. Raymond Gao, Yutao Liu, R. Rand Allingham, Rohit Varma, Stuart MacGregor, Arthur J. Sit, John H. Fingert, Nisha Sondhi, Baojian Fan, Cornelia M. van Duijn, Nagasamy Soumittra, Calvin C P Pang, Doug Rhee, Paul R. Lichter, P. Ferdinamarie Sharmila, Douglas E. Gaasterland, Sarangapani Sripriya, Murray H. Brilliant, Jamie E Craig, Ching-Yu Cheng, Aniket Mishra, Alex W. Hewitt, Ananth C. Viswanathan, Janey L. Wiggs, Peter Kraft, Jost B. Jonas, Tanja Zeller, Louis R. Pasquale, Gudmar Thorleifsson, Ronnie George, Robert Ritch, Chiea Chuen Khor, Christopher J Hammond
Přispěvatelé: Clinical Genetics, Ophthalmology, Epidemiology, Obstetrics & Gynecology, Psychiatry
Rok vydání: 2018
Předmět:
Zdroj: Investigative Ophthalmology & Visual Science
Investigative Ophthalmology and Visual Science, 59(6), 2495-2502. Association for Research in Vision and Ophthalmology Inc.
George, R J & Wiggs, J L 2018, ' Family-based Genome-wide Association Study of South Indian Pedigrees Supports WNT7B as a Central Corneal Thickness Locus ', Investigative Ophthalmology & Visual Science . https://doi.org/10.1167/iovs.17-23536
ISSN: 1552-5783
0146-0404
DOI: 10.1167/iovs.17-23536
Popis: 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.
Databáze: OpenAIRE
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