Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

Alexander A. Navarini; Michael A. Simpson; Michael Weale; Jo Knight; Isabelle Carlavan; Pascale Reiniche; David A. Burden; Alison Layton; Veronique Bataille; Michael Allen; Robert Pleass; Andrew Pink; Daniel Creamer; John English; Stephanie Munn; Shernaz Walton; Carolyn Willis; Sophie Deret; Johannes J. Voegel; Tim Spector; Catherine H. Smith; Richard C. Trembath; Jonathan N. Barker; Acne Genetic Study Grp

doi:10.1038/ncomms5020

Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

Alexander A. Navarini, Michael A. Simpson, Michael Weale, Jo Knight, Isabelle Carlavan, Pascale Reiniche, David A. Burden, Alison Layton, Veronique Bataille, Michael Allen, Robert Pleass, Andrew Pink, Daniel Creamer, John English, Stephanie Munn, Shernaz Walton, Carolyn Willis, Sophie Deret, Johannes J. Voegel, Tim SpectorCatherine H. Smith, Richard C. Trembath^*, Jonathan N. Barker, Acne Genetic Study Grp

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

62 Citations (Scopus)

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, P-combined = 3.23 x 10(-11), odds ratio (OR) = 1.20), 5q11.2 (rs38055, P-combined = 4.58 x 10(-9), OR = 1.17) and 1q41 (rs1159268, P-combined = 4.08 x 10(-8), OR = 1.17). All three loci contain genes linked to the TGF beta 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 TGF beta-mediated signalling in susceptibility to acne.

Original language	English
Article number	4020
Number of pages	6
Journal	Nature Communications
Volume	5
Issue number	1
Early online date	13 Jun 2014
DOIs	https://doi.org/10.1038/ncomms5020
Publication status	Published - 13 Jun 2014

Keywords

TGF-BETA
GROWTH
DIFFERENTIATION
PROLIFERATION
CELLS
GENE
SKIN
STRATIFICATION
KERATINOCYTES
TRANSCRIPTION

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10.1038/ncomms5020

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Navarini, A. A., Simpson, M. A., Weale, M., Knight, J., Carlavan, I., Reiniche, P., Burden, D. A., Layton, A., Bataille, V., Allen, M., Pleass, R., Pink, A., Creamer, D., English, J., Munn, S., Walton, S., Willis, C., Deret, S., Voegel, J. J., ... Acne Genetic Study Grp (2014). Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris. Nature Communications, 5(1), Article 4020. https://doi.org/10.1038/ncomms5020

@article{f10ec5d299734c60b2d5106cc18028bf,

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, P-combined = 3.23 x 10(-11), odds ratio (OR) = 1.20), 5q11.2 (rs38055, P-combined = 4.58 x 10(-9), OR = 1.17) and 1q41 (rs1159268, P-combined = 4.08 x 10(-8), OR = 1.17). All three loci contain genes linked to the TGF beta 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 TGF beta-mediated signalling in susceptibility to acne.",

keywords = "TGF-BETA, GROWTH, DIFFERENTIATION, PROLIFERATION, CELLS, GENE, SKIN, STRATIFICATION, KERATINOCYTES, TRANSCRIPTION",

author = "Navarini, {Alexander A.} and Simpson, {Michael A.} and Michael Weale and Jo Knight and Isabelle Carlavan and Pascale Reiniche and Burden, {David A.} and Alison Layton and Veronique Bataille and Michael Allen and Robert Pleass and Andrew Pink and Daniel Creamer and John English and Stephanie Munn and Shernaz Walton and Carolyn Willis and Sophie Deret and Voegel, {Johannes J.} and Tim Spector and Smith, {Catherine H.} and Trembath, {Richard C.} and Barker, {Jonathan N.} and {Acne Genetic Study Grp}",

year = "2014",

month = jun,

day = "13",

doi = "10.1038/ncomms5020",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

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Navarini, AA, Simpson, MA , Weale, M, Knight, J, Carlavan, I, Reiniche, P, Burden, DA, Layton, A, Bataille, V, Allen, M, Pleass, R, Pink, A, Creamer, D, English, J, Munn, S, Walton, S, Willis, C, Deret, S, Voegel, JJ, Spector, T , Smith, CH , Trembath, RC , Barker, JN & Acne Genetic Study Grp 2014, 'Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris', Nature Communications, vol. 5, no. 1, 4020. https://doi.org/10.1038/ncomms5020

TY - JOUR

T1 - Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

AU - Navarini, Alexander A.

AU - Simpson, Michael A.

AU - Weale, Michael

AU - Knight, Jo

AU - Carlavan, Isabelle

AU - Reiniche, Pascale

AU - Burden, David A.

AU - Layton, Alison

AU - Bataille, Veronique

AU - Allen, Michael

AU - Pleass, Robert

AU - Pink, Andrew

AU - Creamer, Daniel

AU - English, John

AU - Munn, Stephanie

AU - Walton, Shernaz

AU - Willis, Carolyn

AU - Deret, Sophie

AU - Voegel, Johannes J.

AU - Spector, Tim

AU - Smith, Catherine H.

AU - Trembath, Richard C.

AU - Barker, Jonathan N.

AU - Acne Genetic Study Grp

PY - 2014/6/13

Y1 - 2014/6/13

N2 - 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, P-combined = 3.23 x 10(-11), odds ratio (OR) = 1.20), 5q11.2 (rs38055, P-combined = 4.58 x 10(-9), OR = 1.17) and 1q41 (rs1159268, P-combined = 4.08 x 10(-8), OR = 1.17). All three loci contain genes linked to the TGF beta 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 TGF beta-mediated signalling in susceptibility to acne.

AB - 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, P-combined = 3.23 x 10(-11), odds ratio (OR) = 1.20), 5q11.2 (rs38055, P-combined = 4.58 x 10(-9), OR = 1.17) and 1q41 (rs1159268, P-combined = 4.08 x 10(-8), OR = 1.17). All three loci contain genes linked to the TGF beta 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 TGF beta-mediated signalling in susceptibility to acne.

KW - TGF-BETA

KW - GROWTH

KW - DIFFERENTIATION

KW - PROLIFERATION

KW - CELLS

KW - GENE

KW - SKIN

KW - STRATIFICATION

KW - KERATINOCYTES

KW - TRANSCRIPTION

U2 - 10.1038/ncomms5020

DO - 10.1038/ncomms5020

M3 - Article

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4020

ER -

Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris

Abstract

Keywords

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