Assessing genotypic, phenotypic, and polygenic risk associations of autoimmune comorbidities in FinnGen patients with vitiligo
Recommended Citation
Chen S, Pavlovsky M, Reeve MP, Passeron T, Hamzavi I, Ghosh P, Basey V, Adiri R. Assessing genotypic, phenotypic, and polygenic risk associations of autoimmune comorbidities in FinnGen patients with vitiligo. J Invest Dermatol 2025; 145(12).
Document Type
Conference Proceeding
Publication Date
7-21-2025
Publication Title
J Invest Dermatol
Keywords
Pfizer, Pfizer USA, Tel Aviv University, Sackler Faculty of Medicine, Universite Cote d'Azur, Henry Ford Health System, Pfizer United Kingdom, Microsoft, MICROSOFT ISRAEL, Pfizer Israel
Abstract
Using the FinnGen biobank this study aimed to investigate the genetic, phenotypic, and polygenic risk associations of autoimmune comorbidities in patients aged ≥12 years with vitiligo. A genome-wide association study (GWAS) aimed to detect genetic variants linked to vitiligo. Phenome-wide association studies (PheWAS) compared patients with vitiligo to matched controls, and patients with vitiligo in the top 20% of ≥1 predefined vitiligo polygenic risk score (PGS) distribution to patients with vitiligo not in the top 20% of any vitiligo PGS distribution using predefined endpoints. Analysis of the impact of PGS on the risk of comorbidities compared all patients with vitiligo and patients in the top 20% of ≥1 vitiligo PGS distribution. 629 patients with vitiligo and 388,760 controls were included. The GWAS confirmed previously reported associations at HLA-DQA1, HLA-A, and AFM loci. Vitiligo conferred phenome-wide significant increased risk of alopecia areata, atopic dermatitis, autoimmune hypothyroidism, thyroid gland disorders, rheumatoid arthritis, and vitamin B12 deficiency anemia vs controls. Patients in the top 20% of ≥1 vitiligo PGS had a significantly increased risk of type 1 diabetes and thyroid gland disorders compared to those not in the top 20% of any vitiligo PGS. In the PGS analysis, vitiligo conferred significantly higher risk of developing psoriasis, T1D, RA, and hypothyroidism, and lower risk of developing multiple sclerosis compared to controls. These associations were stronger among the top 20% of PGS distributions. This is the first study to highlight genetic and polygenic contributions to vitiligo and its autoimmune comorbidities.
Volume
145
Issue
12
