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Nat Commun. 2018 Dec 12;9(1):5075. doi: 10.1038/s41467-018-07459-5.

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

Author information

1
Department of Medical and Molecular Genetics, School of Basic & Medical Biosciences, King's College London, London, SE1 9RT, UK.
2
Departement of Dermatology, University Hospital of Zurich and University of Zurich, CH-8091, Zurich, Switzerland.
3
St John's Institute of Dermatology, School of Basic & Medical Biosciences, King's College London, London, SE1 9RT, UK.
4
NIHR Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust (SLaM) & Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, SE5 8AF, UK.
5
Social Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, SE5 8AF, UK.
6
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, G12 8TA, UK.
7
Department of Dermatology, Harrogate and District Foundation Trust, Harrogate, HG2 7SX, UK.
8
Twin Research and Genetic Epidemiology Unit, School of Basic & Medical Biosciences, King's College London, London, SE1 7EH, UK.
9
Research Department, Galderma R&D, Sophia Antipolis, 06410 Biot, France.
10
St John's Institute of Dermatology, School of Basic & Medical Biosciences, King's College London, London, SE1 9RT, UK. jonathan.barker@kcl.ac.uk.
11
Department of Medical and Molecular Genetics, School of Basic & Medical Biosciences, King's College London, London, SE1 9RT, UK. michael.simpson@kcl.ac.uk.

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.

PMID:
30542056
PMCID:
PMC6290788
DOI:
10.1038/s41467-018-07459-5
[Indexed for MEDLINE]
Free PMC Article

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