Assessment of familial risk in patients with hidradenitis suppurativa

Bruinsma, Raquel L; Fajgenbaum, Kristen; Yang, Yuhong; Melendez-Gonzalez, Maria del Mar; Mohlke, Karen L.; Li, Yun; Sayed, Christopher

doi:10.1111/bjd.19664

Cited by 6 publications

(7 citation statements)

References 8 publications

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“…17,18 In 2021, a US study estimated a sibling recurrence risk of HS to be 19Á9%. 43 In the present study this risk was 8Á2% (n = 14/170), a result contributable to the seven concordant MZ twin pairs. The three prior estimates all relied on anamnestic information and not confirmed clinical diagnoses.…”

Section: Discussionsupporting

confidence: 46%

“…Approximately 30–40% of Western patients with HS report at least one affected first‐degree relative 17,18 . In 2021, a US study estimated a sibling recurrence risk of HS to be 19·9% 43 . In the present study this risk was 8·2% ( n = 14/170), a result contributable to the seven concordant MZ twin pairs.…”

Section: Discussionmentioning

confidence: 44%

“…The three prior estimates all relied on anamnestic information and not confirmed clinical diagnoses. 17,18,43 A lower first-degree relative risk would be expected when the HS phenotype is based on clinical diagnoses, an assertion confirmed in a recent nationwide Danish registry study that reported a familial risk of HS for first-degree relatives of 3Á8%. 11 Ultimately, the disparity need not be incompatible, but is rather a consequence of the underdiagnosis of HS cobbled with the uncertainty of anamnestic information, as a family history of HS has been linked to earlier disease onset, 18 which, in turn, is linked to severity, 44 and as severe cases are most likely to be referred to dermatology departments.…”

Section: Discussionmentioning

confidence: 77%

“…In the present study this risk was 8·2% ( n = 14/170), a result contributable to the seven concordant MZ twin pairs. The three prior estimates all relied on anamnestic information and not confirmed clinical diagnoses 17,18,43 . A lower first‐degree relative risk would be expected when the HS phenotype is based on clinical diagnoses, an assertion confirmed in a recent nationwide Danish registry study that reported a familial risk of HS for first‐degree relatives of 3·8% 11 .…”

Section: Discussionmentioning

confidence: 93%

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Evidence of gene–gene interaction in hidradenitis suppurativa: a nationwide registry study of Danish twins

Andersen

Clemmensen

Larsen

et al. 2022

British Journal of Dermatology

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Summary 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. Objectives To estimate the relative importance of genetic and environmental factors underlying susceptibility to HS. Methods Via the Danish Twin Registry and the Danish National Patient Registry we pulled together information on zygosity with that of HS status. Cases of HS were identified by the International Classification of Diseases (ICD)‐8 (705·91) and ICD‐10 (L73·2). Heritability was assessed by the classic biometric model and the possibility of gene–gene interaction via the multilocus modelling approach. Results Among 100 044 registered twins, we found 170 twins (from 163 pairs) diagnosed with HS. The seven concordant pairs were all monozygotic. Monozygotic twins had a case‐wise concordance rate of 28% [95% confidence interval (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. Conclusions This twin study was substantially larger and employed a more valid phenotype than previous studies. Genetics account for the majority of 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 single‐nucleotide polymorphism (SNP)–SNP level should be implemented in future HS genome‐wide association studies.

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Section: Discussionsupporting

confidence: 46%

Section: Discussionmentioning

confidence: 44%

Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 93%

See 2 more Smart Citations

Evidence of gene–gene interaction in hidradenitis suppurativa: a nationwide registry study of Danish twins

Andersen

Clemmensen

Larsen

et al. 2022

British Journal of Dermatology

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“…Although HS is a heritable trait (Bruinsma et al, 2021), only a minority of patients with apparent familial disease have underlying GSC pathogenic variation. Data from twin registries suggests that the primary mechanism underlying HS involves gene-gene and gene-environment interactions rather than monogenic variation (Straalen et al, 2020;Kjaersgaard Andersen et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Interpreting the spectrum of gamma-secretase complex missense variation in the context of hidradenitis suppurativa—An in-silico study

2022

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Hidradenitis suppurativa (HS) is a disease of the pilosebaceous unit characterized by recurrent nodules, abscesses and draining tunnels with a predilection to intertriginous skin. The pathophysiology of HS is complex. However, it is known that inflammation and hyperkeratinization at the hair follicle play crucial roles in disease manifestation. Genetic and environmental factors are considered the main drivers of these two pathophysiological processes. Despite a considerable proportion of patients having a positive family history of disease, only a minority of patients suffering from HS have been found to harbor monogenic variants which segregate to affected kindreds. Most of these variants are in the ɣ secretase complex (GSC) protein-coding genes. In this manuscript, we set out to characterize the burden of missense pathogenic variants in healthy reference population using large scale genomic dataset thereby providing a standard for comparing genomic variation in GSC protein-coding genes in the HS patient cohort.

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Genetic Variants Associated With Hidradenitis Suppurativa

et al. 2023

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ImportanceHidradenitis suppurativa (HS) is a common and severely morbid chronic inflammatory skin disease that is reported to be highly heritable. However, the genetic understanding of HS is insufficient, and limited genome-wide association studies (GWASs) have been performed for HS, which have not identified significant risk loci.ObjectiveTo identify genetic variants associated with HS and to shed light on the underlying genes and genetic mechanisms.Design, Setting, and ParticipantsThis genetic association study recruited 753 patients with HS in the HS Program for Research and Care Excellence (HS ProCARE) at the University of North Carolina Department of Dermatology from August 2018 to July 2021. A GWAS was performed for 720 patients (after quality control) with controls from the Add Health study and then meta-analyzed with 2 large biobanks, UK Biobank (247 cases) and FinnGen (673 cases). Variants at 3 loci were tested for replication in the BioVU biobank (290 cases). Data analysis was performed from September 2021 to December 2022.Main Outcomes and MeasuresMain outcome measures are loci identified, with association of P &lt; 1 × 10−8 considered significant.ResultsA total of 753 patients were recruited, with 720 included in the analysis. Mean (SD) age at symptom onset was 20.3 (10.57) years and at enrollment was 35.3 (13.52) years; 360 (50.0%) patients were Black, and 575 (79.7%) were female. In a meta-analysis of the 4 studies, 2 HS-associated loci were identified and replicated, with lead variants rs10512572 (P = 2.3 × 10−11) and rs17090189 (P = 2.1 × 10−8) near the SOX9 and KLF5 genes, respectively. Variants at these loci are located in enhancer regulatory elements detected in skin tissue.Conclusions and RelevanceIn this genetic association study, common variants associated with HS located near the SOX9 and KLF5 genes were associated with risk of HS. These or other nearby genes may be associated with genetic risk of disease and the development of clinical features, such as cysts, comedones, and inflammatory tunnels, that are unique to HS. New insights into disease pathogenesis related to these genes may help predict disease progression and novel treatment approaches in the future.

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Assessment of familial risk in patients with hidradenitis suppurativa

Abstract: Six-year follow-up of vitiligo patients successfully treated with autologous non-cultured melanocyte-keratinocyte transplantation.

Cited by 6 publications

References 8 publications

Evidence of gene–gene interaction in hidradenitis suppurativa: a nationwide registry study of Danish twins

Evidence of gene–gene interaction in hidradenitis suppurativa: a nationwide registry study of Danish twins

Interpreting the spectrum of gamma-secretase complex missense variation in the context of hidradenitis suppurativa—An in-silico study

Genetic Variants Associated With Hidradenitis Suppurativa

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