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Gene interaction analysis of psoriasis in Chinese Han population.

ABSTRACT: Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by excessive proliferation of keratinocytes. It has a strong genetic predisposition; gene-gene interactions are important genetic models for common diseases. In this study, we explore pair-wise interactions among SNPs contributing to psoriasis susceptibility. We first performed gene interactions with exome-sequencing, next, we analyzed gene interactions combining the exome sequencing data with the targeted sequencing data. After we sequenced HLA region, we analyzed gene interactions including HLA regions and non-HLA regions. We found interactions between HLA regions were significant. We observed significant interactions between HLA-C*06:02 and rs118179173 (snp31443520; p = 8.21 × 10-20 , OR = 0.22) and between HLA-C*06:02 and HLA-B:AA67 (p = 1.22 × 10-12 , OR = 0.45). This study provides evidence that HLA is the most important susceptibility region on the risk of psoriasis and interactions that occur in this region are still significant.

SUBMITTER: Xu Q

PROVIDER: S-EPMC9034666 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Gene interaction analysis of psoriasis in Chinese Han population.

Xu Qiongqiong Q Zheng Xiaodong X Mao Yiwen Y Chen Weiwei W Chen Shirui S Zhang Hui H Zhen Qi Q Li Bao B Yong Liang L Ge Huiyao H Yu Yafen Y Zhang Ruixue R Cao Lu L Cheng Hui H Wang Wenjun W Sun Liangdan L

Molecular genetics & genomic medicine 20220330 5

<h4>Background/aims</h4>Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by excessive proliferation of keratinocytes. It has a strong genetic predisposition; gene-gene interactions are important genetic models for common diseases. In this study, we explore pair-wise interactions among SNPs contributing to psoriasis susceptibility.<h4>Methods</h4>We first performed gene interactions with exome-sequencing, next, we analyzed gene interactions combining the exome sequen ...[more]

PMID: 35352505

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Project description:Psoriasis is a chronic inflammatory skin disease related to immune, whose complexity of molecular mechanisms is still not fully clear. RNA sequencing has been widely applied in various fields including biological medicine. According to the bioinformatics analysis of differential genes, biomarkers and drug targets have been discovered for the diagnosis and treatment of diseases. Besides, the pathological mechanisms of disease and functions of gene can be evaluated. In the present study, we report the application of RNA sequencing in skin tissues from psoriatic and healthy persons. By obtaining 2139 differential expressed genes (DEGs), 208 significantly differential GO terms and 44 significantly differential pathways were generated. We found that the functions of DEGs were mainly related to cell cycle, inflammatory, virus, immune response and metabolic process.The major pathways included cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, chemokine signaling pathway, cell cycle, metabolic pathways, ribosome, peroxisome, steroid biosynthesis and biosynthesis of unsaturated fatty acids. Furthermore, co-expression network was constructed to identify core genes and relations between genes. we considered genes with high values of degree and k-core difference in the co-expression network as core genes, such as IFNG, IL26, TLR3, PRKCQ, TLR4, CD274, CDK1 and IL17A. We chose CD274, an important immune checkpoint, to evaluate its regulatory mechanisms. Candidate genes related to CD274 were evaluated by the co-expression network analysis, and the relations between CD274 and candidate genes were validated in epidermal keratinocytes. Finally, IFNG and CDK1 inhibitor (indirubin) were found increasing the expression levels of CD274. In addition, indirubin was confirmed to attenuate mouse psoriasis-like skin lesion with the mechanisms related to CD274. In conclusion, this study provides us a comprehensive transcriptome analysis method on psoriasis to identify core genes and explore the important regulatory functions of genes.

Project description:BackgroundPrevious studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data.MethodsWe obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore.ResultsWe included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants (h2SNP = 29% ± 5.0%, p = 2.00 × 10-8), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen (HLA) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10-16). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum.LimitationsOur sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region.ConclusionWe found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways.

Dataset Information

Gene interaction analysis of psoriasis in Chinese Han population.

Publications

Gene interaction analysis of psoriasis in Chinese Han population.

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