Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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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 - Déret, Sophie
AU - Voegel, Johannes J.
AU - Spector, Tim
AU - Smith, Catherine H.
AU - Trembath, Richard C.
AU - Barker, Jonathan N. W. N.
AU - Acne Genetic Study Group
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, 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.
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, 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.
KW - Acne Vulgaris
KW - Adult
KW - Case-Control Studies
KW - DNA-Binding Proteins
KW - Female
KW - Follistatin
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Genotype
KW - Humans
KW - Male
KW - Polymorphism, Single Nucleotide
KW - Transcription Factors
KW - Transforming Growth Factor beta2
KW - Young Adult
U2 - 10.1038/ncomms5020
DO - 10.1038/ncomms5020
M3 - Journal article
C2 - 24927181
VL - 5
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 4020
ER -