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 2895 7 49, corresponding to a familial risk of 73 (953; 133) times that of the background population. The biometrical modelling suggested a heritability of 0.80 (95.67; 0.93), and the multilocus index estimate was 230 (95 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.