Genome-wide association meta-analysis identifies 29 new acne susceptibility loci

Abstract

Acne vulgaris is a highly heritable skin disorder that primarily impacts facial skin. Severely inflamed lesions may leave permanent scars that have been associated with long-term psychosocial consequences. Here, we perform a GWAS meta-analysis comprising 20,165 individuals with acne from nine independent European ancestry cohorts. We identify 29 novel genome-wide significant loci and replicate 14 of the 17 previously identified risk loci, bringing the total number of reported acne risk loci to 46. Using fine-mapping and eQTL colocalisation approaches, we identify putative causal genes at several acne susceptibility loci that have previously been implicated in Mendelian hair and skin disorders, including pustular psoriasis. We identify shared genetic aetiology between acne, hormone levels, hormone-sensitive cancers and psychiatric traits. Finally, we show that a polygenic risk score calculated from our results explains up to 5.6% of the variance in acne liability in an independent cohort.

Fig. 1. Manhattan plot showing genome-wide significant loci associated with acne (20,165 cases, 595,231 controls).

Axes contain a point for each genetic variant passing QC ordered by chromosome and base position on the x-axis, with −log10(P-value) of association (two-sided Z-test, not adjusted for multiple comparisons) plotted on the y-axis. Blue indicates variants within previously established loci and red indicates variants within novel loci. Pink line indicates genome-wide significance threshold (P = 5 × 10⁻⁸).

Fig. 2. Genetic correlation and latent causal variable analysis between acne and other complex traits.

All analyses were conducted using GWAS summary statistic data from 935 complex traits in the CTG-VL platform. a Black circles represent point estimates of LD score-based genetic correlations. Error bars indicate 95% confidence intervals. b Colour bar indicates strength and direction of genetic correlation where red indicates a negative correlation and blue a positive correlation. Red line indicates significance threshold for multiple testing (FDR < 5%). CI confidence intervals, GCP Genetic causal proportion.

Fig. 3. Acne PRS analysis and prediction.

Top panels show the difference in distributions of mean acne PRSs between individuals that report no acne (grey) to those that report having mild, moderate or severe acne (orange), those that report only moderate or severe acne (green) or those that report only having severe acne (purple). P-values were calculated using a two-sided Student’s t-test. Bottom panels depict the corresponding increase in predictive ability of the acne PRS in these different case groups using receiver operating characteristic (ROC) curves. AUC Area under the curve.