RESUMO
Background: It was reported that educational attainment and household income are associated with oropharyngeal cancer. However, whether such an association is causal is still unknown. Methods: The Mendelian randomization (MR) design was performed to disentangle their causal relationship. Initially, genetic variants proxied for educational attainment and household income were extracted from the largest genome-wide association studies (GWAS), and two oropharyngeal GWAS datasets were used in the discovery and validation stages separately. A reverse MR analysis was carried out to judge whether oropharyngeal cancer affects educational attainment and household income. The results from the two stages were combined using meta-analysis. The heterogeneity and horizontal pleiotropy were appraised using several methods. Results: All selected genetic variants were valid. In the discovery stage, genetically elevated years of education might decrease the risk of oropharyngeal cancer (IVW OR = 0.148 [0.025, 0.872], p-value = 0.035), while such a result became insignificant in the validation stage (IVW p-value >0.05). Household income cannot change the risk of oropharyngeal cancer at both stages. The reverse MR suggested that oropharyngeal cancer should slightly alter household income (IVW OR = 1.001 [1.000, 1.003], p-value = 0.036) in the discovery set, but the result cannot be replicated in the validation stage. The meta-analysis did not find any significant results either. The results were also assessed by sensitivity analyses, and there was no heterogeneity or horizontal pleiotropy in the analyses. The statistical powers were all above 80% at the discovery stage. Conclusions: There should be no causal association between educational attainment, household income, and oropharyngeal cancer.
RESUMO
Background: Associations have been reported between sleep and irritable bowel syndrome (IBS). However, whether there exists a causation between them is still unknown. Methods: We employed the Mendelian randomization (MR) design to explore the causal relationship between sleep and IBS. All genetic associations with sleep-related traits reached genome-wide significance (p-value < 5 × 10-8). The genetic associations with IBS were obtained from two independent large genome-wide association studies (GWAS), where non-FinnGen GWAS was in the discovery stage and FinnGen GWAS was in the validation stage. Primarily, the inverse-variance weighted method was employed to estimate the causal effects, and a meta-analysis was performed to combine the MR estimates. Results: In the discovery, we observed that genetic liability to the "morning" chronotype could lower the risk of IBS [OR = 0.81 (0.76, 0.86)]. Also, the genetic liability to insomnia can increase the risk of IBS [OR = 2.86 (1.94, 4.23)] and such causation was supported by short sleep duration. In the validation stage, only insomnia displayed statistical significance [OR = 2.22 (1.09, 4.51)]. The meta-analysis suggested two genetically-determined sleep exposures can increase the risk of IBS, including insomnia [OR = 2.70 (1.92, 3.80)] and short sleep duration [OR = 2.46 (1.25, 4.86)]. Furthermore, the multivariable MR analysis suggested insomnia is an independent risk factor for IBS after adjusting for chronotype [OR = 2.32 (1.57, 3.43)] and short sleep duration [OR = 1.45 (1.13, 1.85)]. IBS cannot increase the risk of insomnia in the reverse MR analysis. Conclusion: Genetic susceptibility to insomnia can increase the risk of IBS, and improving sleep quality, especially targeting insomnia, can help to prevent IBS.
RESUMO
Laryngeal squamous cell carcinoma (LSCC) is a common aggressive head and neck squamous cell carcinoma (HNSCC) and racial disparities have been reported to exist in it. However, its molecular mechanism and associated ethnic specificity are still unclear. Here, we leveraged mRNA expression data from 2 gene expression omnibus datasets (GSE142083 & GSE117005) of Chinese samples and the cancer genome atlas (TCGA) datasets of Caucasian samples to demonstrate the expression signature of LSCC. The GSE142083 dataset was used as the discovery set since it had 53 pairs of LSCC tissues and matched adjacent normal tissues, and the GSE117005 dataset was treated as the validation set with 5 pairs of tissues. Differential gene expression analysis and enrichment pathway analysis were performed. Besides, we employed weighted gene co-expression network analysis to identify hub genes in validated pathways. The TCGA datasets were used to evaluate ethnic specificity. Immunohistochemistry (IHC) was employed to further validate the hub gene. Overall, the IL-17 signaling pathway was significantly enriched for upregulated genes in two Chinese datasets while not in TCGA datasets; and IL17RC, MAPK3, S100A8, MMP3, CXCL8, and TNFA1P3 were hub genes regulating such pathway. Therein, IL17RC might be the most important one and the IHC results displayed that the IL17RC gene upregulated in the LSCC tissue. IL-17 signaling pathway has an ethnicity-specific effect in LSCC where it is upregulated in the Chinese while not in the Caucasians and IL17RC might play a key role. Targeting genes located in the IL-17 signaling pathway may be beneficial for Chinese LSCC patients.
