Genetic predisposition to neurodegenerative diseases and risk of stroke: A Mendelian randomization study.

Background: Traditional epidemiological studies suggested that Neurodegenerative diseases (ND) might correlate with stroke. We intend to explore whether the two most common neurodegenerative diseases [Alzheimer's disease (AD) and Parkinson's disease (PD)] are causally associated with stroke and its subtypes. Methods: Two-sample Mendelian Randomization (MR) method was used to explore the causal relationships. Candidate genetic instrumental variables (IVs) for AD and PD were collected from the genome-wide association studies (GWAS) in European populations. The inverse-variance weighted (IVW) method was the primary method of MR analysis, and the weighted median method was supplementary. In addition, the MR-Egger method and the MR-PRESSO test were used as well. Results: We found no causal effects of AD on stroke, Ischemic stroke (IS), or Intracerebral hemorrhage (ICH). As for PD and stroke, our preliminary results showed PD could causally influence the risk of stroke [odds ratio (OR): 1.04; 95% confidence interval (CI): 1.02-1.07; P = 0.001 by the IVW method], although the alternative method did not support this result. We identified the positive causal relationship between PD and the risk of IS (OR = 1.04; 95% CI: 1.02-1.07; P = 0.001 by the IVW method), and the alternative MR methods produced similar results. The present study found there was no causal relationship between PD and ICH. Conclusion: This study found a causal relationship between genetic susceptibility to PD and the incidence of stroke (especially IS) in the European population; however, there was no causal relation between AD and stroke risk.

Hip Osteoarthritis and the Risk of Lacunar Stroke: A Two-Sample Mendelian Randomization Study.

Whether hip osteoarthritis (OA) could increase the risk of lacunar stroke (LS) is not well understood. This two-sample Mendelian randomization (MR) study aimed to investigate in depth the effect of genetically predicted hip OA on LS risk. Hip OA-related instrumental variables (IVs) were selected from a genome-wide association study (GWAS) of 393,873 individuals. The summary data of LS were obtained from a GWAS meta-analysis, including 16,030 cases and 248,929 controls. We used the inverse-variance weighted (IVW) as the primary MR analysis method. Moreover, the weighted-median, MR-Egger regression, and the MR pleiotropy residual sum and outlier (MR-PRESSO) test were supplementary methods. The sensitivity analysis was performed using the leave-one-out test. We identified the positive causal relationship between hip OA and the risk of LS (odds ratio [OR] = 1.20, 95% confidence interval [CI]: 1.07, 1.36; p = 0.002 using the IVW method). The weighted median method provided similar results. There was no evidence of directed pleiotropy, and sensitivity analysis results were stable, suggesting the robustness of our study. This study showed a causal effect of hip OA on the risk of LS, and more efforts should be made to explore the potential mechanisms in the future.

Associations of MALAT1 and its functional single nucleotide polymorphisms with cancer.

BACKGROUND: Systematic research on the associations between vital single nucleotide polymorphisms (SNPs) in MALAT1 and cancer risk was still lacking. Thus, we performed this study. MATERIALS AND METHODS: The literature searches were until April 1, 2022. The pooled association-analysis results were assessed by odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) in three genetic models. In addition, we explored the potential functions of MALAT1 and its vital SNPs based on several public websites. RESULTS: Eighteen articles about four SNPs (rs619586, rs664589, rs1194338, and rs3200401) involving 11,843 cancer cases and 14,682 controls were collected. Rs619586, rs664589, and rs1194338 were associated with cancer risk (all P-value < 0.05). Each SNP of the three was significantly related to the risk of colorectal cancer (CRC), and rs619586 correlated with hepatocellular carcinoma (HCC) risk (all P-value < 0.05). The three SNPs might affect the transcription factor, promoter, or enhancer functions. MALAT1 expressed significantly higher in CRC and HCC than in normal tissues. The respective area under the receiver operating characteristic curve of MALAT1 for CRC and HCC patients was 0.783 and 0.864. Moreover, survival analysis indicated that MALAT1 might be a potential prognostic marker of CRC and HCC (all relevant P-value < 0.05). CONCLUSIONS: The functional SNPs in MALAT1 correlated with cancer risk. MALAT1 and its vital functional SNPs might be potential biomarkers for predicting the risk and prognosis of two types of cancer, especially CRC. Further investigations are needed to confirm our present findings.