Nearly 30 Novel Acne Risk Loci Identified in New Meta-analysis

Researchers performed a meta-analysis of genome-wide association studies of over 20,000 patients with acne, identifying 29 novel genome-wide significant acne novel susceptibility loci.

In addition to replicating previously identified acne susceptibility loci, researchers of a recent study have uncovered more than 2 dozen new risk loci. Their findings, say the group, offer a “transformational” increase in the understanding of the genetic underpinnings of acne.

The researchers, publishing their findings in Nature Communications, performed a meta-analysis of genome-wide association studies of over 20,000 patients with acne, identifying 29 novel genome-wide significant acne novel susceptibility loci.

Among 2 of these novel loci, the researchers were able to pinpoint a single putative causal variant: rs1256580 at the TGFB2 locus and rs260643—located in a transcription factor binding site in a region of open chromatin within intron 5 of EDAR—at 2q12.3.

“At several of the newly identified acne risk loci, we find evidence of the importance of the structure and morphology of the hair follicle in disease susceptibility,” detailed the researchers. “There are strong parallels between the phenotypic consequences of the allelic series of variation at the EDAR locus and the previously implicated risk locus at WNT10A. At both of these loci, acne susceptibility, hair morphology, and ectodermal dysplasia all result from genetic variation that impacts the function of the respective genes.”

To identify other putative causal genes, the researchers used fine-mapping and expression quantitative trait loci (eQTL) colocalization approaches, including the colocalization of acne association signals with skin eQTL signals, identification of protein-coding variation within the 95% credible set, and bioinformatics approaches to identifying genes of related biological functions located in the proximity of multiple associated loci.

The combination of approaches showed putative causal genes at multiple loci previously implicated in Mendelian hair and skin disorders. Among the findings was EDNRA as a potential causal gene at the acne risk locus at 4q31.22 and that CSTA is a putative causal gene at 3q21.1, with the latter finding suggesting an importance of cell–cell adhesion processes in the skin in acne susceptibility.

In addition to the 29 novel loci identified, the researchers were also able to replicate 14 of 17 previously identified acne susceptibility loci from prior molecular genetic studies. Fifteen of these loci have been reported to have an effect in European populations while the remaining 2 have been reported to have an effect in a Han Chinese population.

“We failed to replicate the 2 acne risk loci previously reported in the Han Chinese population, 1q24.2 and 11p11.2, with neither of the reported lead variants reaching statistical significance in our meta-analysis (rs7531806 at 1q24.2, P = .336; rs747650 at 11p11.2, P = .0785) and minimal evidence of effect in our separate cohorts,” explained the researchers. “The third previously reported acne susceptibility locus for which we do not observe an association at genome-wide significance is located at 2q14.2. However, we observe evidence of a sub–genome-wide significant effect of the lead variant, rs1092479, consistent with the previously reported magnitude and direction on acne risk (odds ratio, 1.06; P = 9.84 × 10−6).”

Their results, they concluded, both represent “a transformational increase in our understanding of the genetic base of acne” and signify that additional studies are needed to further understand and establish “the biological processes through which genetic risk is mediated.”


Mitchell BL, Saklatvala JR, Dand N, et al. Genome-wide association meta-analysis identifies 29 new acne susceptibility loci. Nat Commun. Published online February 7, 2022. doi:10.1038/s41467-022-28252-5

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