Association analysis of exome variants and refraction, axial length, and corneal curvature in a European–American population

Candelaria Vergara, Samantha M. Bomotti, Cristian Valencia, Barbara E.K. Klein, Kristine E. Lee, Ronald Klein, Alison P. Klein, Priya Duggal

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Refractive errors, myopia, and hyperopia are common visual disorders greatly affecting older individuals. Refraction is determined by genetic factors but only a small percentage of its variation has been explained. We performed a genetic association analysis with three ocular phenotypes: spherical equivalent (a continous measure of refraction), axial length, and corneal curvature in 1,871 European–Americans from the Beaver Dam Eye Study. Individuals were genotyped on the Illumina exome array and imputed to the Haplotype Reference Consortium reference panel. After increasing the number of analyzed variants in targeted protein-coding regions 10-fold via imputation, we confirmed associations for two previously known loci with corneal curvature (chr4q12, rs2114039; g.55092626T > C, β = −0.03 (95% confidence interval [CI]): −0.06, −0.01, P value = 0.01) and spherical equivalent (chr15q14, rs634990; g.35006073T > C, β = −0.27, 95% CI: −0.45, −0.09, P value = 3.79 × 10−3). Despite increased single nucleotide polymorphism (SNP) density, we did not detect any novel significant variants after correction for multiple comparisons. In summary, we confirmed two previous loci associated with corneal curvature and spherical equivalent in a European–American population highlighting the potential biological role of those regions in these traits.

Original languageEnglish (US)
Pages (from-to)1973-1979
Number of pages7
JournalHuman mutation
Volume39
Issue number12
DOIs
StatePublished - Dec 2018

Keywords

  • Haplotype Reference Consortium
  • axial length
  • corneal curvature
  • exome array
  • imputation
  • refraction
  • spherical equivalent

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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