Dataset Information

SNP-SNP interactions between WNT4 and WNT5A were associated with obesity related traits in Han Chinese Population.

ABSTRACT: Considering the biological roles of WNT4 and WNT5A involved in adipogenesis, we aimed to investigate whether SNPs in WNT4 and WNT5A contribute to obesity related traits in Han Chinese population. Targeted genomic sequence for WNT4 and WNT5A was determined in 100 Han Chinese subjects and tag SNPs were selected. Both single SNP and SNP?×?SNP interaction association analyses with body mass index (BMI) were evaluated in the 100 subjects and another independent sample of 1,627 Han Chinese subjects. Meta-analyses were performed and multiple testing corrections were carried out using the Bonferroni method. Consistent with the Genetic Investigation of ANthropometric Traits (GIANT) dataset results, we didn't detect significant association signals in single SNP association analyses. However, the interaction between rs2072920 and rs11918967, was associated with BMI after multiple testing corrections (combined P?=?2.20?×?10-4). The signal was also significant in each contributing data set. SNP rs2072920 is located in the 3'-UTR of WNT4 and SNP rs11918967 is located in the intron of WNT5A. Functional annotation results revealed that both SNPs might be involved in transcriptional regulation of gene expression. Our results suggest that a combined effect of SNPs via WNT4-WNT5A interaction may affect the variation of BMI in Han Chinese population.

SUBMITTER: Dong SS

PROVIDER: S-EPMC5341019 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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SNP-SNP interactions between WNT4 and WNT5A were associated with obesity related traits in Han Chinese Population.

Dong Shan-Shan SS Hu Wei-Xin WX Yang Tie-Lin TL Chen Xiao-Feng XF Yan Han H Chen Xiang-Ding XD Tan Li-Jun LJ Tian Qing Q Deng Hong-Wen HW Guo Yan Y

Scientific reports 20170308

Considering the biological roles of WNT4 and WNT5A involved in adipogenesis, we aimed to investigate whether SNPs in WNT4 and WNT5A contribute to obesity related traits in Han Chinese population. Targeted genomic sequence for WNT4 and WNT5A was determined in 100 Han Chinese subjects and tag SNPs were selected. Both single SNP and SNP × SNP interaction association analyses with body mass index (BMI) were evaluated in the 100 subjects and another independent sample of 1,627 Han Chinese subjects. M ...[more]

PMID: 28272483

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Project description:BackgroundGene-gene interactions may be partly responsible for complex traits such as obesity. Increasing evidence suggests that the renin-angiotensin system (RAS) contributes to the etiology of obesity. How the epistasis of genes in the RAS contributes to obesity is still under research. We aim to evaluate the contribution of RAS-related gene interactions to a predisposition of obesity in a Chinese population.Methodology and principal findingsWe selected six single nucleotide polymorphisms (SNPs) located in angiotensin (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AGTR1), MAS1, nitric oxide synthase 3 (NOS3) and the bradykinin B2 receptor gene (BDKRB2), and genotyped them in 324 unrelated individuals with obesity (BMI ≥ 28 kg/m(2)) and 373 non-obese controls (BMI 18.5 to <24 kg/m(2)) from a large scale population-based cohort. We analyzed gene-gene interactions among 6 polymorphic loci using the Generalized Multifactor Dimensionality Reduction (GMDR) method, which has been shown to be effective for detecting gene-gene interactions in case-control studies with relatively small samples. Then we used logistic regression models to confirm the best combination of loci identified in the GMDR. It showed a significant gene-gene interaction between the rs220721 polymorphism in the MAS1 gene and the rs1799722 polymorphism in the gene BDKB2R. The best two-locus combination scored 9 for cross-validation consistency and 9 for sign test (p = 0.0107). This interaction showed the maximum consistency and minimum prediction error among all gene-gene interaction models evaluated. Moreover, the combination of the MAS1 rs220721 and the BDKRB2 rs1799722 was associated with a significantly increased risk of obesity (OR 1.82, CI 95%: 1.15-2.88, p = 0.0103).Conclusions and significanceThese results suggest that the SNPs from the RAS-related genes may contribute to the risk of obesity in an interactive manner in a Chinese population. The gene-gene interaction may serve as a novel area for obesity research.

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.

Dataset Information

SNP-SNP interactions between WNT4 and WNT5A were associated with obesity related traits in Han Chinese Population.

Publications

SNP-SNP interactions between WNT4 and WNT5A were associated with obesity related traits in Han Chinese Population.

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