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; The Acne Genetic Study Group; Carolyn Willis; Sophie Déret; Johannes J. Voegel; Catherine H. Smith; Richard C. Trembath; Jonathan N. Barker; Adam  Ferguson

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, The Acne Genetic Study Group, Carolyn Willis, Sophie Déret, Johannes J. VoegelCatherine H. Smith (Lead / Corresponding author), Richard C. Trembath (Lead / Corresponding author), Jonathan N. Barker (Lead / Corresponding author), Adam Ferguson

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 × 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 TGFß 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 TGFß-mediated signalling in susceptibility to acne.

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

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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., The Acne Genetic Study Group, Willis, C., Déret, S., ... Ferguson, A. (2014). Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris. Nature Communications, 5, Article 4020. https://doi.org/10.1038/ncomms5020

@article{cdae064cc35c4ec3aa5ce3ad5fc9e9e2,

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 × 10-11 , odds ratio (OR)=1.20), 5q11.2 (rs38055, Pcombined =4.58 × 10-9, OR=1.17) and 1q41 (rs1159268, Pcombined =4.08 × 10-8, OR=1.17). All three loci contain genes linked to the TGF{\ss} 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{\ss}-mediated signalling in susceptibility to acne.",

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 {The Acne Genetic Study Group} and Carolyn Willis and Sophie D{\'e}ret and Voegel, {Johannes J.} and Smith, {Catherine H.} and Trembath, {Richard C.} and Barker, {Jonathan N.} and V. Akhras and A. Alexandroff and A. Anstey and J. Azad and O. Aziz and D. Baudry and N. Burrows and A. Butt and P. Cartwright and A. Chapman and T. Clayton and S. Cliff and W. Cunliffe and T. Cutler and B. Daly and E. Damian and A. Darvay and C. DeGiovanni and A. Downs and M. Duckworth and C. Dwyer and Adam Ferguson and C. Fleming and Z. Fox and E. Frazer-Andrews and J. Gonzalez and M. Goodfield and R. Graham",

note = "Updated online 03 July 2014",

year = "2014",

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day = "13",

doi = "10.1038/ncomms5020",

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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, The Acne Genetic Study Group, Willis, C, Déret, S, Voegel, JJ, Smith, CH, Trembath, RC, Barker, JN & Ferguson, A 2014, 'Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris', Nature Communications, vol. 5, 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 - The Acne Genetic Study Group

AU - Willis, Carolyn

AU - Déret, Sophie

AU - Voegel, Johannes J.

AU - Smith, Catherine H.

AU - Trembath, Richard C.

AU - Barker, Jonathan N.

AU - Akhras, V.

AU - Alexandroff, A.

AU - Anstey, A.

AU - Azad, J.

AU - Aziz, O.

AU - Baudry, D.

AU - Burrows, N.

AU - Butt, A.

AU - Cartwright, P.

AU - Chapman, A.

AU - Clayton, T.

AU - Cliff, S.

AU - Cunliffe, W.

AU - Cutler, T.

AU - Daly, B.

AU - Damian, E.

AU - Darvay, A.

AU - DeGiovanni, C.

AU - Downs, A.

AU - Duckworth, M.

AU - Dwyer, C.

AU - Ferguson, Adam

AU - Fleming, C.

AU - Fox, Z.

AU - Frazer-Andrews, E.

AU - Gonzalez, J.

AU - Goodfield, M.

AU - Graham, R.

N1 - Updated online 03 July 2014

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

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U2 - 10.1038/ncomms5020

DO - 10.1038/ncomms5020

M3 - Article

C2 - 24927181

AN - SCOPUS:84902458172

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 4020

ER -

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

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