Genome‑wide Association Study and Polygenic Risk Scores Predict Psoriasis and Its Shared Phenotypes in Taiwan

Overview

Journal Mol Med Rep

Specialty Molecular Biology

Date 2024 May 17

PMID 38757301

Authors

Jai-Sing Yang

Ting-Yuan Liu

Hsing-Fang Lu

Shih-Chang Tsai

Wen-Ling Liao

Yu-Jen Chiu

Yu-Wen Wang

Fuu-Jen Tsai

Affiliations

Soon will be listed here.

Abstract

Psoriasis is a chronic inflammatory dermatological disease, and there is a lack of understanding of the genetic factors involved in psoriasis in Taiwan. To establish associations between genetic variations and psoriasis, a genome‑wide association study was performed in a cohort of 2,248 individuals with psoriasis and 67,440 individuals without psoriasis. Using the ingenuity pathway analysis software, biological networks were constructed. Human leukocyte antigen (HLA) diplotypes and haplotypes were analyzed using Attribute Bagging (HIBAG)‑R software and chi‑square analysis. The present study aimed to assess the potential risks associated with psoriasis using a polygenic risk score (PRS) analysis. The genetic association between single nucleotide polymorphisms (SNPs) in psoriasis and various human diseases was assessed by phenome‑wide association study. METAL software was used to analyze datasets from China Medical University Hospital (CMUH) and BioBank Japan (BBJ). The results of the present study revealed 8,585 SNPs with a significance threshold of P<5x10‑8, located within 153 genes strongly associated with the psoriasis phenotype, particularly on chromosomes 5 and 6. This specific genomic region has been identified by analyzing the biological networks associated with numerous pathways, including immune responses and inflammatory signaling. HLA genotype analysis indicated a strong association between and in a Taiwanese population. Based on our PRS analysis, the risk of psoriasis associated with the SNPs identified in the present study was quantified. These SNPs are associated with various dermatological, circulatory, endocrine, metabolic, musculoskeletal, hematopoietic and infectious diseases. The meta‑analysis results indicated successful replication of a study conducted on psoriasis in the BBJ. Several genetic loci are significantly associated with susceptibility to psoriasis in Taiwanese individuals. The present study contributes to our understanding of the genetic determinants that play a role in susceptibility to psoriasis. Furthermore, it provides valuable insights into the underlying etiology of psoriasis in the Taiwanese community.

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References

Liu T, Lin C, Wu H, Wu Y, Chen Y, Liao C . Comparison of multiple imputation algorithms and verification using whole-genome sequencing in the CMUH genetic biobank. Biomedicine (Taipei). 2022; 11(4):57-65. PMC: 8823485. DOI: 10.37796/2211-8039.1302. View

Ishida-Yamamoto A, Furio L, Igawa S, Honma M, Tron E, Malan V . Inflammatory peeling skin syndrome caused by homozygous genomic deletion in the PSORS1 region encompassing the CDSN gene. Exp Dermatol. 2013; 23(1):60-3. DOI: 10.1111/exd.12292. View

Yang J, Liu T, Chen Y, Tsai S, Chiu Y, Liao C . Genome-Wide Association Study of Alopecia Areata in Taiwan: The Conflict Between Individuals and Hair Follicles. Clin Cosmet Investig Dermatol. 2023; 16:2597-2612. PMC: 10519225. DOI: 10.2147/CCID.S428788. View

Gregory A, Dendrou C, Attfield K, Haghikia A, Xifara D, Butter F . TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature. 2012; 488(7412):508-511. PMC: 4268493. DOI: 10.1038/nature11307. View

Zhou X, He Y, Kuang Y, Chen W, Zhu W . and Alleles are Associated with Acitretin Response in Patients with Psoriasis. Front Biosci (Landmark Ed). 2022; 27(9):266. DOI: 10.31083/j.fbl2709266. View

Wu C, Hu H, Li C, Chou Y, Chang Y . Comorbidity profiles of psoriasis in Taiwan: A latent class analysis. PLoS One. 2018; 13(2):e0192537. PMC: 5800685. DOI: 10.1371/journal.pone.0192537. View

Cai M, Huang H, Ran D, Zheng X, Wen L, Zhu Z . HLA-C*01:02 and HLA-A*02:07 Confer Risk Specific for Psoriatic Patients in Southern China. J Invest Dermatol. 2019; 139(9):2045-2048.e4. DOI: 10.1016/j.jid.2019.02.027. View

Sokolik R, Gebura K, Iwaszko M, Swierkot J, Korman L, Wiland P . Significance of association of HLA-C and HLA-E with psoriatic arthritis. Hum Immunol. 2014; 75(12):1188-91. DOI: 10.1016/j.humimm.2014.10.005. View

Witoelar A, Jansen I, Wang Y, Desikan R, Gibbs J, Blauwendraat C . Genome-wide Pleiotropy Between Parkinson Disease and Autoimmune Diseases. JAMA Neurol. 2017; 74(7):780-792. PMC: 5710535. DOI: 10.1001/jamaneurol.2017.0469. View

10.

Aractingi S, Briand N, Le Danff C, Viguier M, Bachelez H, Michel L . HLA-G and NK receptor are expressed in psoriatic skin: a possible pathway for regulating infiltrating T cells?. Am J Pathol. 2001; 159(1):71-7. PMC: 1850403. DOI: 10.1016/S0002-9440(10)61675-6. View

11.

Woo J, Lee C . Identification of functional haplotypes in the promoter region of the LST1 gene. Biochem Genet. 2014; 52(7-8):365-71. DOI: 10.1007/s10528-014-9653-x. View

12.

Miao X, Xiang Y, Mao W, Chen Y, Li Q, Fan B . TRIM27 promotes IL-6-induced proliferation and inflammation factor production by activating STAT3 signaling in HaCaT cells. Am J Physiol Cell Physiol. 2019; 318(2):C272-C281. DOI: 10.1152/ajpcell.00314.2019. View

13.

Huang J, Su B, Karhunen V, Gill D, Zuber V, Ahola-Olli A . Inflammatory Diseases, Inflammatory Biomarkers, and Alzheimer Disease: An Observational Analysis and Mendelian Randomization. Neurology. 2022; 100(6):e568-e581. PMC: 9946179. DOI: 10.1212/WNL.0000000000201489. View

14.

Zhen Q, Yang Z, Wang W, Li B, Bai M, Wu J . Genetic Study on Small Insertions and Deletions in Psoriasis Reveals a Role in Complex Human Diseases. J Invest Dermatol. 2019; 139(11):2302-2312.e14. DOI: 10.1016/j.jid.2019.03.1157. View

15.

Byrne L, Toland A . Polygenic Risk Scores in Prostate Cancer Risk Assessment and Screening. Urol Clin North Am. 2021; 48(3):387-399. DOI: 10.1016/j.ucl.2021.03.007. View

16.

Lamore S, Wondrak G . Zinc pyrithione impairs zinc homeostasis and upregulates stress response gene expression in reconstructed human epidermis. Biometals. 2011; 24(5):875-90. PMC: 4169675. DOI: 10.1007/s10534-011-9441-6. View

17.

Cheng Y, Lu C, Hsu Y, Tsai F, Bau D, Tsai S . and studies of taiwan chingguan yihau (NRICM101) on TNF-α/IL-1β-induced human lung cells. Biomedicine (Taipei). 2022; 12(3):56-71. PMC: 9629402. DOI: 10.37796/2211-8039.1378. View

18.

Yin X, Low H, Wang L, Li Y, Ellinghaus E, Han J . Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility. Nat Commun. 2015; 6:6916. PMC: 4423213. DOI: 10.1038/ncomms7916. View

19.

Nair R, Callis Duffin K, Helms C, Ding J, Stuart P, Goldgar D . Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet. 2009; 41(2):199-204. PMC: 2745122. DOI: 10.1038/ng.311. View

20.

Hao L, Kraft P, Berriz G, Hynes E, Koch C, Korategere V Kumar P . Development of a clinical polygenic risk score assay and reporting workflow. Nat Med. 2022; 28(5):1006-1013. PMC: 9117136. DOI: 10.1038/s41591-022-01767-6. View