The current landscape of psoriasis genetics in 2020

Abstract

Psoriasis is an immune-mediated disease associated with skin and joint inflammation that affects large proportions of populations worldwide. It is a heritable disease: individuals' genetic backgrounds modulate their susceptibility. In genetics, multiple human leukocyte antigen (HLA) genes are most strongly associated with the risk of psoriasis, especially HLA-C*06:02. In the last 10 years, large-scale genome-wide association studies (GWASs) of psoriasis have been conducted in multiple populations, and these have substantially increased the number of genetic loci associated with psoriasis susceptibility (n > 80). Understanding the genetic background of psoriasis is important for understanding the disease's biology, identifying clinical biomarkers, discovering novel drug targets, and accelerating the journey towards personalized medicine. However, the application of whole-genome and long-read sequencing technology in psoriasis genetic analysis is still developing. Moreover, achieving practical strategies for translating psoriasis risk-associated genetic variants into functional annotations and clinical applications remains challenging. In this review, we detail the current and future landscape of psoriasis genetics and introduce the cutting-edge use of large-scale GWAS data, especially in the Japanese population.

Keywords: HLA; Mendelian randomization; drug repositioning; genome-wide association study; psoriasis.