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

Pubmed ID: 32141793

Pubmed Central ID: PMC7483204

Journal: Ocular immunology and inflammation

Publication Date: Feb. 17, 2021

MeSH Terms: Humans, Male, Adult, Female, Case-Control Studies, United States, Middle Aged, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genotype, DNA, Follow-Up Studies, Morbidity, Sarcoidosis, Cell Adhesion Molecules, Adaptor Proteins, Signal Transducing, Eye Diseases, Black or African American, Autoimmunity, Guanylate Kinases, HLA-DRB1 Chains

Grants: R01 HL113326, P30 GM110766, U54 GM104938

Authors: Iannuzzi MC, Rybicki BA, Levin AM, Adrianto I, Garman L, Montgomery CG, Li C, Pezant N, Pastori A, Savoy KA

Cite As: Garman L, Pezant N, Pastori A, Savoy KA, Li C, Levin AM, Iannuzzi MC, Rybicki BA, Adrianto I, Montgomery CG. 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. Epub 2020 Mar 6.

Studies:

Abstract

<b>Purpose</b>: Identify genes associated with ocular sarcoidosis (OS).<b>Methods</b>: We genotyped 1.1 million genetic variants to identify significant OS associations, defined as those that achieved <i>p</i> &lt; 5 × 10<sup>-8</sup> 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.<b>Results</b>: 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 <i>MAGI1</i> and include transcription factor binding sites and expression quantitative trait loci. Our EA cohort, while showing similar effect sizes at variants within <i>MAGI1</i>, had no significant variants. Association analysis of <i>HLA-DRB1</i> alleles confirmed association to OS in EA to *04:01.<b>Conclusion</b>: Our results support organ-specific genetic risk in OS in a compelling candidate, <i>MAGI1</i>, known to be associated with barrier function and autoimmunity.