Genome-Wide Association Study of Ocular Sarcoidosis Confirms HLA Associations and Implicates Barrier Function and Autoimmunity in African Americans

Ocul Immunol Inflamm. 2021 Feb 17;29(2):244-249. doi: 10.1080/09273948.2019.1705985. Epub 2020 Mar 6.

Abstract

Purpose: Identify genes associated with ocular sarcoidosis (OS).Methods: We genotyped 1.1 million genetic variants to identify significant OS associations, defined as those that achieved p < 5 × 10-8 in a genome-wide comparison of OS cases to healthy controls in our European- or African-American cohorts (EA, AA). Potential functional roles of all associated variants were assessed.Results: Eight significant non-HLA variants were found in AA OS cases compared to healthy controls and confirmed as at least suggestive when comparing OS to non-OS cases. Seven of these were within MAGI1 and include transcription factor binding sites and expression quantitative trait loci. Our EA cohort, while showing similar effect sizes at variants within MAGI1, had no significant variants. Association analysis of HLA-DRB1 alleles confirmed association to OS in EA to *04:01.Conclusion: Our results support organ-specific genetic risk in OS in a compelling candidate, MAGI1, known to be associated with barrier function and autoimmunity.

Keywords: GWAS; HLA-DRB1*04:01; MAGI1; Sarcoidosis; ocular.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Autoimmunity / genetics
  • Black or African American / genetics*
  • Case-Control Studies
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • DNA / genetics
  • Eye Diseases / ethnology
  • Eye Diseases / genetics*
  • Eye Diseases / immunology
  • Female
  • Follow-Up Studies
  • Genome-Wide Association Study / methods*
  • Genotype
  • Guanylate Kinases / genetics*
  • Guanylate Kinases / metabolism
  • HLA-DRB1 Chains / genetics*
  • HLA-DRB1 Chains / immunology
  • Humans
  • Male
  • Middle Aged
  • Morbidity / trends
  • Polymorphism, Single Nucleotide*
  • Sarcoidosis / ethnology
  • Sarcoidosis / genetics*
  • Sarcoidosis / immunology
  • United States / epidemiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Adhesion Molecules
  • HLA-DRB1 Chains
  • DNA
  • Guanylate Kinases
  • MAGI1 protein, human