Inter‐Relater Reliability of Phenotypes, and Exploratory Genotype‐ Phenotype Analysis in Inherited Hidradenitis Suppurativa

Abstract

Background

Genotype‐phenotype correlation is a statistical relationship that measures correlation between the presence of a physical trait with a group of similar mutations but is dependent upon reliable phenotyping. It can provide information regarding disease pathogenesis, future disease progression, severity or activity. Such indicators would be valuable in Hidradenitis Suppurativa.

Aims and Methods

This study aimed to assess the inter‐rater reliability of hidradenitis suppurativa clinical phenotypes and perform exploratory genotype‐phenotype correlation in cases of hidradenitis suppurativa with identified sequence variants. Linkage disequilibrium between variants was assessed. Genotype‐Phenotype correlations were explored using Spearman correlation coefficients. Inter‐rater reliability was calculated using Cohen's kappa. Correlation between phenotype classifications was assessed using χ² statistic.

Results

43 sequence variants with clinical information were identified. Clinical phenotypes were classified as LC2 (n=29, 67.4%), Scarring Folliculitis (n=18, 41.8%), atypical (n=38, 88.3%) and nodular (n=26, 60.5%). LC1 phenotype was associated with Regular (χ2=41.289, p<0.0001) and Typical (χ2=29.013, p<0.0001) phenotypes. Cohen's kappa was highest for Van der Zee (0.815), followed by Martorell (0.813), Naasan (0.774) and Canoui (0.435) classifications. High linkage disequilibrium was seen between variants of Han Chinese pedigrees. No significant genotype‐phenotype correlations were identified.

Conclusions

These findings may be influenced by selection, publication bias and the assumption that HS is a monogenic disorder. The poor inter‐rater reliability of existing phenotype measures suggests limited utility of existing measures. Further investigations into the correlation of clinical phenotypes with inflammatory biomarkers may aid in prognostic efforts for this disease.

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