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 9 independent European ancestry cohorts.
We identify 29 novel genome-wide statistically-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.
…Genetic correlations and causal relationships of acne with other traits: Assuming a population prevalence of 30% for acne, the genome-wide statistically-significant acne risk loci explain an estimated 6.01% of the variance in acne liability. However, estimation of heritability explained by all common SNPs, ie. the SNP-based heritability, indicates that 22.95% (s.e. = 0.02) of the variance in acne liability is explained by common genetic variation across the genome.
We used this extensive polygenicity to examine the genetic correlation and potential causal relationship between acne and a series of 935 human diseases and traits, finding 45 traits with statistically-significant genetic correlations (Supplementary Data 7). As has been previously observed, there is evidence of genetic correlation between acne and Crohn’s Disease (rg = 0.19, s.e. = 0.07) (Figure 2a). We also observe evidence of shared genetic architecture with disease traits that are phenotypically associated with acne; this includes breast cancer (rg = 0.16, s.e. = 0.05) and psychiatric disorders such as schizophrenia (rg = 0.18, s.e. = 0.06) and bipolar disorder (rg = 0.12, s.e. = 0.05). There is also evidence of asymmetry in the observed genetic correlation between acne and endogenous testosterone and bilirubin levels, breast cancer, joint pain and headaches (Figure 2b, Supplementary Data 7).
