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
Journal of the American Academy of Dermatology, 2024
Kjærsgaard Andersen R., Stefansdottir L., Riis P., Halldorsson G., Ferkingstad E., Oddsson A., Walters B., Olafsdottir T., Rutsdottir G., Zachariae C., Thomsen S., Brodersen T., Dinh K., Knowlton K., Knight S., Nadauld L., Banasik K., Brunak S., Hansen T., Hjalgrim H., Sørensen E., Mikkelsen C., Ullum H., Nyegaard M., Bruun M., Erikstrup C., Ostrowski S., Eidsmo L., Saunte D., Sigurgeirsson B., Orvar K., Saemundsdottir J., Melsted P., Norddahl G., Sulem P., Stefansson H., Holm H., Gudbjartsson D., Thorleifsson G., Jonsdottir I., Pedersen O., Jemec G., Stefansson K.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases | Pathophysiology | Plasma | O Olink Explore 3072/384 |
Abstract
BACKGROUND
The contributions of genetic and environmental risk factors to hidradenitis suppurativa (HS) are both poorly understood.
OBJECTIVE
To identify sequence variants that associate with HS and determine the contribution of environmental risk factors and inflammatory diseases to HS pathogenesis.
METHODS
A genome-wide association meta-analysis of 4,814 HS cases (Denmark: 1,977; Iceland: 1,266; Finland: 800; UK: 569 and US: 202) and 1.2 million controls, searching for sequence variants associated with HS.
RESULTS
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.LIMITATIONSLimited racial diversity may prevent identification of sequence variants of particular importance in non-Caucasian populations.CONCLUSIONSThese findings demonstrate that genes and pathways involved in epidermal keratinization are the genetic backbone of HS pathology.