Abstrakt
Background: Hidradenitis suppurativa (HS) is a recurrent inflammatory skin disease that, apart from rare causative loss-of-function mutations, has a widely unknown genetic aetiology. Our objective was to estimate the relative importance of genetic and environmental factors underlying HS susceptibility.
Methods: Through the Danish Twin Registry and the Danish National Patient Registry we joined information on zygosity with that of HS status. HS cases were identified by International Code of Diseases 8 (705.91) and 10 (L73.2). Heritability was assessed by the classic biometric model and the possibility of gene-gene interaction through the multi-locus modeling approach.
Results: Amongst 100,044 registered twins, we found 170 twins (from 163 pairs) diagnosed with HS. The seven concordant pairs were all monozygotic, and monozygotic twins had a casewise concordance rate of 28% (95% CI: 7%; 49%), corresponding to a familial risk of 73 (95% CI 13; 133) times that of the background population.
The biometrical modelling suggested a heritability of 0.80 (95% CI 0.67; 0.93), and the multilocus index estimate was 230 (95% CI: 60; 400). This is highly indicative of gene-gene interactions, with the possibility of up to six interacting loci.
Conclusion: This twin study is substantially larger, and employs a more valid phenotype than prior studies. Genetics account for the majority of the HS susceptibility, and HS is most likely caused by gene-gene interactions rather than monogenetic mutations or solely additive genetic factors. New approaches aimed at assessing potential interactions at a SNP-SNP level should be implemented in future HS genome-wide association studies.
Methods: Through the Danish Twin Registry and the Danish National Patient Registry we joined information on zygosity with that of HS status. HS cases were identified by International Code of Diseases 8 (705.91) and 10 (L73.2). Heritability was assessed by the classic biometric model and the possibility of gene-gene interaction through the multi-locus modeling approach.
Results: Amongst 100,044 registered twins, we found 170 twins (from 163 pairs) diagnosed with HS. The seven concordant pairs were all monozygotic, and monozygotic twins had a casewise concordance rate of 28% (95% CI: 7%; 49%), corresponding to a familial risk of 73 (95% CI 13; 133) times that of the background population.
The biometrical modelling suggested a heritability of 0.80 (95% CI 0.67; 0.93), and the multilocus index estimate was 230 (95% CI: 60; 400). This is highly indicative of gene-gene interactions, with the possibility of up to six interacting loci.
Conclusion: This twin study is substantially larger, and employs a more valid phenotype than prior studies. Genetics account for the majority of the HS susceptibility, and HS is most likely caused by gene-gene interactions rather than monogenetic mutations or solely additive genetic factors. New approaches aimed at assessing potential interactions at a SNP-SNP level should be implemented in future HS genome-wide association studies.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | British Journal of Dermatology |
| Vol/bind | 186 |
| Udgave nummer | 1 |
| Sider (fra-til) | 78-85 |
| ISSN | 0007-0963 |
| DOI | |
| Status | Udgivet - jan. 2022 |