Genome-wide meta-analysis implicates mediators of hair follicle development and morphogenesis in risk for severe acne

• Published in: Nature communications Vol. 9; no. 1; pp. 5075 - 8
• Main Authors: Petridis, Christos, Navarini, Alexander A, Dand, Nick, Saklatvala, Jake, Baudry, David, Duckworth, Michael, Allen, Michael H, Curtis, Charles J, Lee, Sang Hyuck, Burden, A David, Layton, Alison, Bataille, Veronique, Pink, Andrew E, Carlavan, Isabelle, Voegel, Johannes J, Spector, Timothy D, Trembath, Richard C, McGrath, John A, Smith, Catherine H, Barker, Jonathan N, Simpson, Michael A
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 12.12.2018; Nature Publishing Group UK; Nature Portfolio
• Subjects: Acne; Acne Vulgaris - genetics; Acne Vulgaris - pathology; Binding sites; Blistering; Chromosome 1; Epidermolysis bullosa; Female; Genetic Predisposition to Disease - genetics; Genetic Variation - genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Gram-Positive Bacterial Infections - microbiology; Gram-Positive Bacterial Infections - pathology; Hair Follicle - growth & development; Humans; Laminin - biosynthesis; Laminin - genetics; Loci; Male; Membrane Proteins - metabolism; Meta-analysis; Morphogenesis; Mutation; Propionibacterium acnes - growth & development; Risk; Semaphorins - genetics; Skin - pathology; Skin diseases; Statistical analysis; Wnt Proteins - genetics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-07459-5

Acne vulgaris is a highly heritable common, chronic inflammatory disease of the skin for which five genetic risk loci have so far been identified. Here, we perform a genome-wide association study of 3823 cases and 16,144 controls followed by meta-analysis with summary statistics from a previous study, with a total sample size of 26,722. We identify 20 independent association signals at 15 risk loci, 12 of which have not been previously implicated in the disease. Likely causal variants disrupt the coding region of WNT10A and a P63 transcription factor binding site in SEMA4B. Risk alleles at the 1q25 locus are associated with increased expression of LAMC2, in which biallelic loss-of-function mutations cause the blistering skin disease epidermolysis bullosa. These findings indicate that variation affecting the structure and maintenance of the skin, in particular the pilosebaceous unit, is a critical aspect of the genetic predisposition to severe acne.