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

Petridis, C. et al. (2018) Genome-wide meta-analysis implicates mediators of hair follicle development and morphogenesis in risk for severe acne. Nature Communications, 9, 5075. (doi: 10.1038/s41467-018-07459-5) (PMID:30542056) (PMCID:PMC6290788)

Abstract

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.

• Item Type: Articles
• Additional Information: We acknowledge support from the National Institute for Health Research (NIHR), through the Dermatology Clinical Research Network; the NIHR Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London; a research grant from Galderma SA to J.N.B., C.H.S. and M.A.S.; Bruno Bloch, Promedica Foundation and HSM-2 canton of Zurich grant to A.A.N.; the NIHR Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London; capital equipment funding from the Maudsley Charity (Grant Ref. 980) and Guy’s and St Thomas’ Charity (Grant Ref. STR130505).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Burden, Professor David
• Authors: Petridis, C., Navarini, A. A., Dand, N., Saklatvala, J., Baudry, D., Duckworth, M., Allen, M. H., Curtis, C. J., Lee, S. H., Burden, A. D., Layton, A., Bataille, V., Pink, A. E., Carlavan, I., Voegel, J. J., Spector, T. D., Trembath, R. C., McGrath, J. A., Smith, C. H., Barker, J. N., and Simpson, M. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Nature Communications 9(1):5075
• Publisher Policy: Reproduced under a Creative Commons Licence