April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Family-based Genome-wide Association Study in South Indian Consanguineous Pedigrees Identifies an Association between WNT7B and Central Corneal Thickness
Author Affiliations & Notes
  • Xueli Chen
    Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA
  • Baojian Fan
    Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA
  • P. Ferdina Marie Sharmila
    SNONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India
  • N. Soumittra
    SNONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India
  • S. Sripriya
    SNONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, India
  • D. s. Friedman
    Johns Hopkins Medical School, Wilmer Eye Institute, Baltimore, MD
  • L. Vijaya
    Medical Research Foundation, Sankara Nethralaya, Chennai, India
  • Jonathan Haines
    Center for Human Genetic Research, Vanderbilt University School of Medicine, Nashville, TN
  • Ronnie J George
    Medical Research Foundation, Sankara Nethralaya, Chennai, India
  • Janey L Wiggs
    Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA
  • Footnotes
    Commercial Relationships Xueli Chen, None; Baojian Fan, None; P. Ferdina Marie Sharmila, None; N. Soumittra, None; S. Sripriya, None; D. s. Friedman, None; L. Vijaya, None; Jonathan Haines, None; Ronnie George, None; Janey Wiggs, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 6408. doi:https://doi.org/
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      Xueli Chen, Baojian Fan, P. Ferdina Marie Sharmila, N. Soumittra, S. Sripriya, D. s. Friedman, L. Vijaya, Jonathan Haines, Ronnie J George, Janey L Wiggs; Family-based Genome-wide Association Study in South Indian Consanguineous Pedigrees Identifies an Association between WNT7B and Central Corneal Thickness. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6408. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Central corneal thickness (CCT) is a highly heritable quantitative trait that is a risk factor of primary open angle glaucoma. The identification of genetic factors affecting CCT will provide insights into the mechanisms underlying the association between CCT and glaucoma. Although case-control population-based genome-wide association studies (GWAS) have identified several loci associated with CCT, family-based GWAS can have sufficient power to detect contributing variants with a smaller overall sample. The purpose of this study is to use consanguineous pedigrees from South India for family-based association studies for CCT.

Methods: CCT was measured for 240 members of 16 Indian consanguineous pedigrees using an ultrasonic pachymeter. CCT was measured in triplicate and the average value was used. Genotyping was performed using the Illumina HumanOmni2.5 SNP arrays. 1,223,314 SNPs were analyzed for association with CCT using the score test in MERLIN (v1.1.2). Sanger sequencing was applied for confirmation of the genotypes from SNP arrays.

Results: Using genome-wide genotype data a family-based association study was conducted for CCT. The best evidence for association was found in the WNT7B region. 9 of 57 SNPs within the WNT7B gene were associated with CCT (p < 0.05), including the top SNP rs9330813 (p = 1.71×10-7) and a SNP rs62226057 located in the WNT7B promoter region (p = 0.00998). rs62226057 is evolutionarily conserved and is located within a DNase I hypersensitivity site suggesting that it may influence expression on WNT7B.

Conclusions: Our results suggest that SNPs in the WNT7B gene region are associated with CCT in this dataset. The associated SNPs are located in the 5’ regulatory region suggesting that the associated variants could influence gene expression. WNT7B is a member of the WNT signaling pathway previously shown to participate in the regulation of proliferation of human corneal limbal stem cells (LSCs)1. Our results provide additional support for a role for WNT7B in corneal development and in particular the processes that contribute to central corneal thickness. Future studies investigating the effect of the associated variants on WNT7B gene expression would be of interest. 1Nakatsu MN, et al. Wnt/β-catenin signaling regulates proliferation of human cornea epithelial stem/progenitor cells. IOVS. 2011; 52(7):4734-41.

Keywords: 539 genetics • 440 candidate gene analysis • 480 cornea: basic science  
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