Electronic medical records and genomics (eMERGE) network exploration in cataract: several new potential susceptibility loci

Mol Vis. 2014 Sep 19:20:1281-95. eCollection 2014.

Abstract

Purpose: Cataract is the leading cause of blindness in the world, and in the United States accounts for approximately 60% of Medicare costs related to vision. The purpose of this study was to identify genetic markers for age-related cataract through a genome-wide association study (GWAS).

Methods: In the electronic medical records and genomics (eMERGE) network, we ran an electronic phenotyping algorithm on individuals in each of five sites with electronic medical records linked to DNA biobanks. We performed a GWAS using 530,101 SNPs from the Illumina 660W-Quad in a total of 7,397 individuals (5,503 cases and 1,894 controls). We also performed an age-at-diagnosis case-only analysis.

Results: We identified several statistically significant associations with age-related cataract (45 SNPs) as well as age at diagnosis (44 SNPs). The 45 SNPs associated with cataract at p<1×10(-5) are in several interesting genes, including ALDOB, MAP3K1, and MEF2C. All have potential biologic relationships with cataracts.

Conclusions: This is the first genome-wide association study of age-related cataract, and several regions of interest have been identified. The eMERGE network has pioneered the exploration of genomic associations in biobanks linked to electronic health records, and this study is another example of the utility of such resources. Explorations of age-related cataract including validation and replication of the association results identified herein are needed in future studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Cataract / genetics*
  • Cataract / pathology
  • Databases, Nucleic Acid
  • Electronic Health Records / statistics & numerical data*
  • Female
  • Fructose-Bisphosphate Aldolase / genetics*
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genome, Human
  • Genome-Wide Association Study
  • Health Care Costs
  • Humans
  • MAP Kinase Kinase Kinase 1 / genetics*
  • MEF2 Transcription Factors / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci
  • Vereinigte Staaten

Substances

  • Genetic Markers
  • MEF2 Transcription Factors
  • MEF2C protein, human
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human
  • Fructose-Bisphosphate Aldolase