A genome-wide association meta-analysis links hidradenitis suppurativa to common and rare sequence variants causing disruption of the Notch and Wnt/β-catenin signaling pathways.

Abstract

The contributions of genetic and environmental risk factors to hidradenitis suppurativa (HS) are both poorly understood. To identify sequence variants that associate with HS and determine the contribution of environmental risk factors and inflammatory diseases to HS pathogenesis. A genome-wide association meta-analysis of 4814 HS cases (Denmark: 1977; Iceland: 1266; Finland: 800; UK: 569; and US: 202) and 1.2 million controls, searching for sequence variants associated with HS. We found 8 independent sequence variants associating with HS, 6 common and 2 rare (frequency <1%). Four associations point to candidate causal genes, NCSTN, PSENEN, WNT10A, and TMED10, that all map to the Notch and Wnt/β-catenin signaling pathways, involved in epidermal keratinization. Limited racial diversity may prevent identification of sequence variants of particular importance in non-Caucasian populations. These findings demonstrate that genes and pathways involved in epidermal keratinization are the genetic backbone of HS pathology.