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

• Published in: Nature communications Vol. 13; no. 1; pp. 702 - 9
• Main Authors: Mitchell, Brittany L., Saklatvala, Jake R., Dand, Nick, Hagenbeek, Fiona A., Li, Xin, Min, Josine L., Thomas, Laurent, Bartels, Meike, Jan Hottenga, Jouke, Lupton, Michelle K., Boomsma, Dorret I., Dong, Xianjun, Hveem, Kristian, Løset, Mari, Martin, Nicholas G., Barker, Jonathan N., Han, Jiali, Smith, Catherine H., Rentería, Miguel E., Simpson, Michael A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.02.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 45/43; 631/208/205/2138; 692/308/2056; 692/699/4033/4035; Acne; Acne Vulgaris - genetics; Disorders; Gene mapping; Genetic Predisposition to Disease - genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Hair; Humanities and Social Sciences; Humans; Inflammation; Liability; Loci; Meta-analysis; multidisciplinary; Multifactorial Inheritance; Phenotype; Polygenic inheritance; Polymorphism, Single Nucleotide; Psoriasis; Quantitative Trait Loci; Risk; Scars; Science; Science (multidisciplinary); Skin diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28252-5

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. Better understanding of the genetic basis of acne can pave the way to more effective treatments. Here, the authors perform a genome-wide association study meta-analysis of >20,000 cases and identify 29 new acne susceptibility loci, uncovering genetic links to Mendelian hair and skin disorders and other complex traits.