A Transcriptome-Wide Analysis of Psoriasis: Identifying the Potential Causal Genes and Drug Candidates

Author:

Jeong Yeonbin1,Song Jaeseung1ORCID,Lee Yubin1,Choi Eunyoung1,Won Youngtae1,Kim Byunghyuk2,Jang Wonhee1

Affiliation:

1. Department of Life Sciences, Dongguk University, Seoul 04620, Republic of Korea

2. Department of Life Sciences, Dongguk University-Seoul, Goyang 10326, Republic of Korea

Abstract

Psoriasis is a chronic inflammatory skin disease characterized by cutaneous eruptions and pruritus. Because the genetic backgrounds of psoriasis are only partially revealed, an integrative and rigorous study is necessary. We conducted a transcriptome-wide association study (TWAS) with the new Genotype-Tissue Expression version 8 reference panels, including some tissue and multi-tissue panels that were not used previously. We performed tissue-specific heritability analyses on genome-wide association study data to prioritize the tissue panels for TWAS analysis. TWAS and colocalization (COLOC) analyses were performed with eight tissues from the single-tissue panels and the multi-tissue panels of context-specific genetics (CONTENT) to increase tissue specificity and statistical power. From TWAS, we identified the significant associations of 101 genes in the single-tissue panels and 64 genes in the multi-tissue panels, of which 26 genes were replicated in the COLOC. Functional annotation and network analyses identified that the genes were associated with psoriasis and/or immune responses. We also suggested drug candidates that interact with jointly significant genes through a conditional and joint analysis. Together, our findings may contribute to revealing the underlying genetic mechanisms and provide new insights into treatments for psoriasis.

Funder

National Research Foundation of Korea

Korea Environment Industry & Technology Institute

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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