June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Family-based Genome-wide Association Study in South Indian Consanguineous Pedigrees confirms association between ZNF469 and central corneal thickness
Author Affiliations & Notes
  • Baojian Fan
    Dept of Ophthalmology, Harvard Med Sch Massachusetts Eye & Ear Infirmary, Boston, MA
  • N. Soumittra
    Vision Research Foundation, Sankara Nethralaya, Chennai, India
  • Sarangapani Sripriya
    Vision Research Foundation, Sankara Nethralaya, Chennai, India
  • David Friedman
    Ophthalmology, Johns Hopkins Medical School Wilmer Eye Institute, Baltimore, MD
  • Vijaya Lingam
    Medical Research Foundation, Sankara Nethralaya, Chennai, India
  • Jonathan Haines
    Center for Human Genetic Research, Vanderbilt University School of Medicine, Nashville, TN
  • Ronnie George
    Medical Research Foundation, Sankara Nethralaya, Chennai, India
  • Janey Wiggs
    Dept of Ophthalmology, Harvard Med Sch Massachusetts Eye & Ear Infirmary, Boston, MA
  • Footnotes
    Commercial Relationships Baojian Fan, None; N. Soumittra, None; Sarangapani Sripriya, None; David Friedman, alcon (C), bausch & lomb (C), merck (C), Pfizer (C), QLT, Inc (C); Vijaya Lingam, None; Jonathan Haines, Arctic Dx (I), AMD genes (P); Ronnie George, None; Janey Wiggs, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 6209. doi:https://doi.org/
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      Baojian Fan, N. Soumittra, Sarangapani Sripriya, David Friedman, Vijaya Lingam, Jonathan Haines, Ronnie George, Janey Wiggs; Family-based Genome-wide Association Study in South Indian Consanguineous Pedigrees confirms association between ZNF469 and central corneal thickness. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6209. 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 can be a feature of primary open angle glaucoma. Case-control and population-based genome-wide association studies (GWAS) have identified several loci associated with CCT. While these are effective approaches, large sample sizes are required and population stratification can be a confounding factor. Allelic homozygosity in consanguineous pedigrees may enhance additive and/or subtractive effects of quantitative traits, creating greater variation for quantitative trait loci mapping making it possible to use a smaller sample for analysis. Additionally, family-based GWAS are immune to confounding population stratification. The purpose of this study is to use consanguineous pedigrees from South India for family-based association studies for CCT.

Methods: 240 members of 16 Indian consanguineous pedigrees underwent a comprehensive ophthalmic examination for ocular quantitative traits such as intraocular pressure, central corneal thickness and curvature, optic disc size, optic cup size, visual acuity, and axial length. Genotyping was performed using the Illumina HumanOmni2.5-8 platform. After data cleaning, 1,402,532 SNPs were analyzed for association with CCT. A simple linear regression of phenotype on genotype was performed with permutation testing to account for family structure using QFAM in PLINK v1.07.

Results: SNPs located in the 16q24 genomic region near ZNF469 previously associated with CCT were nominally associated with CCT in this population (top SNP rs4072556, p=5.4×10-5). In addition, novel loci on 5q11 (rs880944 near SNX18, p=3×10-6) and 20p12 (rs4813828, p=2×10-6) showed interesting potential association.

Conclusions: Using family-based genome-wide association analysis and consanguineous families from South India, our results confirmed the association between the 16q24 locus containing ZNF469 and central corneal thickness in the South Indian population. Additionally, novel loci on 5q11 and 20p12 were suggested by this analysis, pending confirmation by further studies.

Keywords: 539 genetics • 480 cornea: basic science • 534 gene mapping  
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