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

<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 × 10⁻⁸ 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. <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.