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

Navarini, Alexander A. and Simpson, Michael A. and Weale, Michael and Knight, Jo and Carlavan, Isabelle and Reiniche, Pascale and Burden, David A. and Layton, Alison and Bataille, Veronique and Allen, Michael and Pleass, Robert and Pink, Andrew and Creamer, Daniel and English, John and Munn, Stephanie and Walton, Shernaz and Willis, Carolyn and Déret, Sophie and Voegel, Johannes J. and Spector, Tim and Smith, Catherine H. and Trembath, Richard C. and Barker, Jonathan N. W. N. (2014) Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris. Nature Communications, 5: 4020. ISSN 2041-1723

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.