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

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:

• Sarcoidosis
• GWAS
• ocular
• MAGI1
• HLA-DRB1*04:01

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by the Foundation for Sarcoidosis Research (Chicago, IL), and the National Institutes of Health under Grant [National Heart, Lung, and Blood Institute (NHLBI) - R01HL113326-05, National Institute of General Medical Sciences (NIGMS) - P30 GM110766-01, and National Institute of General Medical Sciences (NIGMS) - U54GM104938-06].