854 GWAS of acne vulgaris among African Americans

Abstract

Acne vulgaris is a prevalent inflammatory skin disease and is among the most common conditions for which patients seek medical care, due in part to the profound effects it has on psychological well-being. Five GWAS have been conducted previously in Asian and Caucasian cohorts, which have identified a total of 17 loci (p<5x10-8). While African Americans are at a higher risk relative to Caucasians and Asians, and also experience worsened prognosis due to higher rates of hyperpigmentation, scarring and keloids, they have not yet been included in any acne GWAS. Here we performed a GWAS in a cohort of African Americans using data from the electronic MEdical Records & GEnomics (eMERGE) network of electronic health records linked to genome-wide variant data (eMERGE project NT227). We used a diagnosis code (ICD-9 706.1) to identify acne cases and controls, whereby patients with 2+ more records of 706.1 were classified as cases and those without any record of 706.1 were classified as controls. After stringent quality control of samples and variants, we used a subset of 40,156 SNPs to assign genetic ancestry to participants. We identified an African American cohort of 570 cases and 14,134 genetically comparable controls (λ=1.01). Association testing of 40 million genetic variants identified a locus at chromosome 3q25.33 (p=4.5x10-9) that has not been identified in previous acne GWAS, and was not associated with acne among genetically European and Asian eMERGE participants. This locus contains IL-12A, a subunit of a potent immunostimulatory cytokine that has been shown to be induced in monocytes upon exposure to P. acnes. Our work has identified a new acne locus that now requires external replication, and implicates a gene with strong biological plausibility. It highlights differences in the genetic architecture of acne across ancestries and suggests that the inclusion of African Americans in future acne studies is imperative.