RESUMO
It has been a long time that the relationship between serum calcium levels and Alzheimer's disease (AD) remains unclear. Until recently, observational studies have evaluated the association between serum calcium levels and the risk of AD, however, reported inconsistent findings. Meanwhile, a Mendelian randomization (MR) study had been conducted to test the causal association between serum calcium levels and AD risk, however, only selected 6 serum calcium SNPs as the instrumental variables. Hence, these findings should be further verified using additional more genetic variants and large-scale genome-wide association study (GWAS) dataset to increase the statistical power. Here, we conduct an updated MR analysis of the causal association between serum calcium levels and the risk of AD using a two-stage design. In discovery stage, we conducted a MR analysis using 14 SNPs from serum calcium GWAS dataset (N = 61,079), and AD GWAS dataset (N = 63,926, 21,982 cases, 41,944 cognitively normal controls). All four MR methods including IVW, weighted median, MR-Egger, and MR-PRESSO showed a reduced trend of AD risk with the increased serum calcium levels. In the replication stage, we performed a MR analysis using 166 SNPs from serum calcium GWAS dataset (N = 305,349), and AD GWAS dataset (N = 63,926, 21,982 cases, 41,944 cognitively normal controls). Only the weighted median indicated that genetically increased serum calcium level was associated with the reduced risk of AD. Hence, additional studies are required to investigate these findings.
RESUMO
Glioblastoma (GBM), originating in the brain, is a universally aggressive malignant tumor with a particularly poor prognosis. Therefore, insight into the critical role of underlying genetic mechanisms is essential to developing new therapeutic approaches. This study aims to identify potential markers with clinical and prognostic significance in GBM. To this end, increasing numbers of differentially expressed RNA have been identified used to construct competitive endogenous RNA networks for prognostic analysis via comparison and analysis of RNA expression levels of tumor and normal tissues in glioblastoma. This analysis demonstrated that the RNA expression patterns of normal and tumor samples were significantly different. Thus, the resulting differentially expressed RNAs were used to construct competitive endogenous RNA (competing endogenous RNA, ceRNA) networks. The functional enrichment indicated mRNAs in the network are critically involved in a variety of biological functions. Additionally, the prognostic analysis suggested 27 lncRNAs, including LOXL1-AS1, AL356414.1, etc., were significantly associated with patient survival. Given the prognostic significance of these 27 lncRNAs in GBM, we sought to classify the samples. Importantly, Kaplan-Meier analysis revealed that survival times varied significantly among the different categories. Overall, these results identify that the candidate lncRNAs are potential prognostic markers of GBM and its corresponding mRNAs may be a potential target for therapy.