Acne vulgaris is a common chronic skin condition characterized by blockage and/or inflammation of the hair follicles and the accompanying sebaceous glands. An estimated 80-90% of teenagers in the Western world are affected by varying degrees of acne, and moderate-to-severe acne affects around 20% of teenagers. Acne is highly genetic, with heritability estimates of ~80% based on studies of first-degree relatives and twins (PMID 23210645, PMID 12485434, PMID 17447973, PMID 12566802).
Three genome-wide association studies for severe cases of acne have been conducted to this date. A 2013 GWAS among 81 cases and 847 controls in European Americans did not identify genome-wide significant SNPs (PMID24114350). In 2014, a two-stage GWAS involving 2916 cases and 4716 controls in the Han Chinese population identified two susceptibility loci at 11p11.2 (rs747650, Pcombined=4.41 × 10−9, OR=1.24; rs1060573, Pcombined=1.28 × 10−8, OR=1.23) and 1q24.2 (rs7531806, Pcombined=1.20 × 10−8, OR=1.22) (PMID 24399259).
Another 2014 GWAS study among 3956 cases and 7102 controls in the United Kingdom identified three loci at 11q13.1 (rs478304, Pcombined=3.23 × 10−11, odds ratio (OR)=1.20), 5q11.2 (rs38055, Pcombined=4.58 × 10−9, OR=1.17) and 1q41 (rs1159268, Pcombined=4.08 × 10−8, OR=1.17) (PMID 24927181). All three loci contain genes implicated in TGFb signaling pathway. In the same study, the authors reported that the expression levels of two of the genes closest to each of the three genome-wide significant SNPs (OVOL1 and TGFB2; <500kb) are reduced in skin biopsies from individuals affected by acne. The two associations reported in the Han Chinese study were not detected in this study.
A number of other genes have been associated with severe acne in smaller size cohorts using candidate approaches. These include TNF, TNFR2, TLR2, IL1A, CYP1A1, CYP17A1, CYP21A2, AR (PMIDS 22835835, 18615253, 20861605 , 20630038, 9557256, 16707883, 9579234, 19218788 ). None were replicated in the GWAS studies.