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- Liu, H, et al.
(författare)
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A putative causality of vitamin D in common diseases: A mendelian randomization study
- 2022
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Ingår i: Frontiers in nutrition. - : Frontiers Media SA. - 2296-861X. ; 9, s. 938356-
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D is considered as a nutrient protecting individuals against an array of diseases based on observational studies. Such a protective effect, however, has not been demonstrated by randomized controlled trials. This study aims to explore a putative causal role of vitamin D in common diseases through a two-sample Mendelian randomization (MR) framework.MethodsCirculating vitamin D was predicted by 41 genetic variants discovered in European populations. Common diseases were verified through two ways, using information from Japanese patients of Biobank Japan and using information from European patients of FinnGen project. We additionally validated the results by replacing vitamin D-associated instrumental variables (IVs) of European population with that of an independent Japanese population and of an independent Indian population. Inverse-variance weighted method was used as the primary analytical approach while a series of MR methods including MR-Egger regression, weighted median, maximum likelihood, MR-PRESSO and multivariate MR were adopted to guarantee MR model assumptions and to detect horizontal pleiotropy.ResultsGenetically predicted vitamin D was significantly associated with an increased risk of Graves' disease (OR = 1.71, 95%CI: 1.25–2.33, P = 0.001) and cataract (OR = 1.14, 95%CI: 1.03–1.28, P = 0.016); while with a decreased risk of esophageal cancer (OR = 0.66, 95%CI: 0.46–0.93, P = 0.019). This significant causal link between vitamin D and cataract was validated replacing IVs identified in the European population with those from Japanese population. No notable associations of vitamin D with other diseases were observed.ConclusionsOur findings indicate a potential causal role of vitamin D in common diseases, which needs further validation.
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- Polewko-Klim, A, et al.
(författare)
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Identification of Candidate Therapeutic Genes for More Precise Treatment of Esophageal Squamous Cell Carcinoma and Adenocarcinoma
- 2022
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Ingår i: Frontiers in genetics. - : Frontiers Media SA. - 1664-8021. ; 13, s. 844542-
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Tidskriftsartikel (refereegranskat)abstract
- The standard therapy administered to patients with advanced esophageal cancer remains uniform, despite its two main histological subtypes, namely esophageal squamous cell carcinoma (SCC) and esophageal adenocarcinoma (AC), are being increasingly considered to be different. The identification of potential drug target genes between SCC and AC is crucial for more effective treatment of these diseases, given the high toxicity of chemotherapy and resistance to administered medications. Herein we attempted to identify and rank differentially expressed genes (DEGs) in SCC vs. AC using ensemble feature selection methods. RNA-seq data from The Cancer Genome Atlas and the Fudan-Taizhou Institute of Health Sciences (China). Six feature filters algorithms were used to identify DEGs. We built robust predictive models for histological subtypes with the random forest (RF) classification algorithm. Pathway analysis also be performed to investigate the functional role of genes. 294 informative DEGs (87 of them are newly discovered) have been identified. The areas under receiver operator curve (AUC) were higher than 99.5% for all feature selection (FS) methods. Nine genes (i.e., ERBB3, ATP7B, ABCC3, GALNT14, CLDN18, GUCY2C, FGFR4, KCNQ5, and CACNA1B) may play a key role in the development of more directed anticancer therapy for SCC and AC patients. The first four of them are drug targets for chemotherapy and immunotherapy of esophageal cancer and involved in pharmacokinetics and pharmacodynamics pathways. Research identified novel DEGs in SCC and AC, and detected four potential drug targeted genes (ERBB3, ATP7B, ABCC3, and GALNT14) and five drug-related genes.
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