Exploration of the causality of frailty index on psoriasis: A Mendelian randomization study

Background Frailty is associated with a variety of diseases, but the relationship between frailty and psoriasis remains unclear. Methods First, we conducted a two‐sample Mendelian randomization based on genome‐wide association studies (GWAS) to investigate genetic causality between frailty index and...

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Published in:Skin research and technology 2024-03, Vol.30 (3), p.e13641-n/a
Main Authors: Lei, Hao, Xing, Zixuan, Chen, Xin, Dai, Yilin, Cheng, Baochen, Wang, Shengbang, Kang, Tong, Wang, Qian, Zhang, Jing, Jia, Jinjing, Zheng, Yan
Format: Article
Language:English
Subjects:
Causality
Dermatology
DQA1 protein
Drb1 protein
eQTLs
Frailty
frailty index
Gene mapping
Genes
GWAS
Heterogeneity
Histocompatibility antigen HLA
mendelian randomization
Nucleotides
Pleiotropy
Proteomes
Psoriasis
Quantitative trait loci
Randomization
Single-nucleotide polymorphism
Skin diseases
Transcriptomes
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Summary:Background Frailty is associated with a variety of diseases, but the relationship between frailty and psoriasis remains unclear. Methods First, we conducted a two‐sample Mendelian randomization based on genome‐wide association studies (GWAS) to investigate genetic causality between frailty index and common diseases in dermatology. Inverse variance weighted was used to estimate causality. Second, expression quantitative trait locus (eQTLs) analysis was conducted to identify the genes affected by Single nucleotide polymorphisms (SNPs). Third, we performed function and pathway enrichment, transcriptome‐wide association studies (TWAS) analysis based on eQTLs. Results It was shown that the rise of frailty index could increase the risk of psoriasis (IVW, beta = 0.916, OR = 2.500, 95%CI:1.418‐4.408, p = 0.002) through Mendelian randomization (MR), and there was no heterogeneity and pleiotropy. There was no causality between the frailty index and other common diseases in dermatology. We found 31 eQTLs based on strongly correlated SNPs in the causality. TWAS analysis found that the expressions of four genes were closely related to psoriasis, including HLA‐DQA1, HLA‐DQA2, HLA‐DRB1 and HLA‐DQB1. Conclusion It suggested that the frailty index had a significant positive causality on the risk of psoriasis, which was well documented by combined genomic, transcriptome, and proteome analyses.
ISSN:0909-752X
1600-0846
DOI:10.1111/srt.13641