Identifying a Genetic Link Between Lung Function and Psoriasis

Introduction: The common genetic underpinnings of psoriasis and pulmonary comorbidities have yet to be explored.

Material and methods: In this cross-sectional study, we investigated the single-nucleotide polymorphisms (SNPs) associated with psoriasis and their relationship with pulmonary function using data from the UK Biobank (UKBB) and the Vanderbilt University Medical Center Biobank (BioVU).

Results: Out of the 63 psoriasis-associated SNPs identified in previous genome-wide association studies within the European population, we successfully identified 53 SNPs, including proxy SNPs in UKBB database. Following adjustments using age and sex, 31 SNPs displayed statistically significant associations with psoriasis. Among these, 16 SNPs exhibited significant associations with forced expiratory volume in 1 s (FEV₁), 14 with forced vital capacity (FVC), and 5 with the FEV₁/FVC ratio in the UKBB. In the validation analysis using the BioVU database, 27 of the 31 psoriasis-associated SNPs were available for examination. Notably, the minor allele of SNP rs8016947 was confirmed to be significant, indicating a reduced risk for psoriasis and improved FEV₁. Similarly, the minor alleles of SNPs rs17716942 and rs8016947 were associated with a reduced risk of psoriasis and enhanced FVC. However, none of the 5 SNPs significantly associated with the FEV₁/FVC ratio in the UKBB displayed significance in the BioVU dataset.

Conclusion: This study has unveiled genetic variants that bridge the realms of psoriasis and lung function. The genes associated with these variants, including IFIH1, Grancalcin gene (GCA), and NFKB inhibitor alpha gene (NFKBIA), regulate innate immune responses, which suggests that immunodysregulation, a central element in psoriasis pathogenesis, may also impact lung function, alluding to a "skin-lung axis."