title: Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris.
abstract: Acne vulgaris (acne) is a common inflammatory disorder of the cutaneous pilo-sebaceous unit. Here we perform a genome-wide association analysis in the United Kingdom, comparing severe cases of acne (n=1,893) with controls (n=5,132). In a second stage, we genotype putative-associated loci in a further 2,063 acne cases and 1,970 controls. We identify three genome-wide significant associations: 11q13.1 (rs478304, Pcombined=3.23 × 10(-11), odds ratio (OR) = 1.20), 5q11.2 (rs38055, P(combined) = 4.58 × 10(-9), OR = 1.17) and 1q41 (rs1159268, P(combined) = 4.08 × 10(-8), OR = 1.17). All three loci contain genes linked to the TGFβ cell signalling pathway, namely OVOL1, FST and TGFB2. Transcripts of OVOL1 and TFGB2 have decreased expression in affected compared with normal skin. Collectively, these data support a key role for dysregulation of TGFβ-mediated signalling in susceptibility to acne.
authors.affiliation: 1] Division of Genetics and Molecular Medicine, King's College London, London SE1 9RT, UK [2].
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Navarini
authors.affiliation: 1] Division of Genetics and Molecular Medicine, King's College London, London SE1 9RT, UK [2].
authors.forename: Michael A
authors.initials: MA
authors.lastname: Simpson
authors.affiliation: 1] Division of Genetics and Molecular Medicine, King's College London, London SE1 9RT, UK [2].
authors.forename: Michael
authors.initials: M
authors.lastname: Weale
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada.
authors.forename: Jo
authors.initials: J
authors.lastname: Knight
authors.affiliation: Scientific Division, Galderma R&D, 06410 Sophia-Antipolis, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Carlavan
authors.affiliation: Scientific Division, Galderma R&D, 06410 Sophia-Antipolis, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Reiniche
authors.affiliation: Department of Dermatology, Western Infirmary, Glasgow G11 6NT, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Burden
authors.affiliation: Department of Dermatology, Harrogate and District Foundation Trust, Harrogate HG2 7SX, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Layton
authors.affiliation: Twin Research and Genetic Epidemiology Unit, Division of Genetics and Molecular Medicine, King's College, London SE1 7EH, UK.
authors.forename: Veronique
authors.initials: V
authors.lastname: Bataille
authors.affiliation: Division of Genetics and Molecular Medicine, King's College London, London SE1 9RT, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Allen
authors.affiliation: St John's Institute of Dermatology, Guy's and St.Thomas' NHS Foundation Trust, London SE1 9RT, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Pleass
authors.affiliation: 1] Division of Genetics and Molecular Medicine, King's College London, London SE1 9RT, UK [2] St John's Institute of Dermatology, Guy's and St.Thomas' NHS Foundation Trust, London SE1 9RT, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pink
authors.affiliation: Department of Dermatology, King's College Hospital NHS Foundation Trust, London SE5 9RS, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Creamer
authors.affiliation: Department of Dermatology, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UJ, UK.
authors.forename: John
authors.initials: J
authors.lastname: English
authors.affiliation: Department of Dermatology, Orpington Hospital, King's College Hospital NHS Foundation Trust, Orpington BR6 9JU, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Munn
authors.affiliation: Hull and East Yorkshire Hospitals, NHS Trust and Hull York Medical School, Hull HU3 2JZ, UK.
authors.forename: Shernaz
authors.initials: S
authors.lastname: Walton
authors.affiliation: Department of Dermatology, Orpington Hospital, King's College Hospital NHS Foundation Trust, Orpington BR6 9JU, UK.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Willis
authors.affiliation: Scientific Division, Galderma R&D, 06410 Sophia-Antipolis, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Déret
authors.affiliation: Scientific Division, Galderma R&D, 06410 Sophia-Antipolis, France.
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Voegel
authors.affiliation: Twin Research and Genetic Epidemiology Unit, Division of Genetics and Molecular Medicine, King's College, London SE1 7EH, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Spector
authors.affiliation: St John's Institute of Dermatology, Guy's and St.Thomas' NHS Foundation Trust, London SE1 9RT, UK.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Smith
authors.affiliation: Hull and East Yorkshire Hospitals, NHS Trust and Hull York Medical School, Hull HU3 2JZ, UK.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Trembath
authors.affiliation: Division of Genetics and Molecular Medicine, King's College London, London SE1 9RT, UK.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Barker
mesh_terms: D000152:Acne Vulgaris / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D038681:Follistatin / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics; D053781:Transforming Growth Factor beta2 / Q000235:genetics; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C503233:FST protein, human; D038681:Follistatin; C490319:OVOL1 protein, human; C509041:TGFB2 protein, human; D014157:Transcription Factors; D053781:Transforming Growth Factor beta2