Rs747650

rs747650 is a variant on chromosome 11p11.2 associated with acne. rs747650-G (reference major allele A, + strand) was identified as a risk allele associated with severe acne in a two-stage genome-wide association study with Han Chinese individuals by He et al. (PMID 24399259). An initial GWAS (1031 cases of severe acne and 1031 selected control subjects without acne) identified 101 SNPs with evidence of association (P<1x10^-4 or P<1x10^-2 located within/near nine candidate susceptibility genes) including rs747650 (p = 8.12x10^-5, OR 95% CI 1.14-1.47). These SNPs were further evaluated in an independent cohort (1860 cases and 3660 controls). The replication round identified 3 SNPs achieving genome-wide significance including rs747650 (p = 9.25x10^-6, OR 95% CI 1.12-1.33) with an overall combined P=4.41x10^-9 / OR 95% CI 1.16-1.34. No significant association for this SNP was found in a similar study in European individuals from the United Kingdom which was sufficiently powered for the reported effect size in the Han Chinese study.

rs747650 is the lead SNP and is located within an intron of C11ORF49. It is unknown whether this variant has any causal influence on severe acne. One hypothesis is that rs747650 may be an eQTL involved in transcriptional regulation, based on ENCODE data indicating a peak density of DNAse hypersensitivity, histone marks and transcription factor ChIP overlapping this locus. He et al. speculates that a neighboring gene DDB2 is a potential candidate gene for acne susceptibility based on its implication in androgen metabolism and inflammation. References: