Objective To analyze the causal relationship between gut microbiota and tic disorder based on Mendelian randomization (MR). Methods A total of 196 known microbiota (9 phyla, 16 classes, 20 orders, 32 families, and 119 genera) in the human intestinal microbiota dataset downloaded from the MiBioGen database were selected as the exposure factors, and the dataset of tic disorder (finn-b-KRA_PSY_TIC) containing 172 patients and 218620 controls was downloaded from the genome-wide association study database as the outcome variable. Inverse variance weighted was used as the main analysis method, and the causal relationship between gut microbiota and tic disorder was evaluated using odds ratio (OR) and its 95% confidence interval (CI). Horizontal pleiotropy was tested by MR-Egger intercept and MR-PRESSO global test, heterogeneity was assessed by Cochran’s Q test, and sensitivity analysis was performed by leave-one-out method. Results Inverse variance weighted results showed that the Family Rhodospirillaceae [OR=0.398, 95%CI (0.191, 0.831), P=0.014], Order Rhodospirillales [OR=0.349, 95%CI (0.164, 0.743), P=0.006], and Parasutterella [OR=0.392, 95%CI (0.171, 0.898), P=0.027] had negative causal relationships with tic disorder. The Genus Lachnospira [OR=8.784, 95%CI (1.160, 66.496), P=0.035] and Candidatus Soleaferrea [OR=2.572, 95%CI (1.161, 5.695), P=0.020] had positive causal relationships with tic disorder. In addition, MR-Egger intercept and MR-PRESSO global test showed no horizontal pleiotropy, Cochran’s Q test showed no heterogeneity, and leave-one-out sensitivity analysis showed the results were stable. Conclusions A causal relationship exists between gut microbiota and tic disorder. The Family Rhodospirillaceae, Order Rhodospirillales, and Parasutterella are associated with a decreased risk of tic disorder, while the Genus Lachnospira and Candidatus Soleaverea can increase the risk of tic disorder.
Objective To explore the causal relationship between heart failure and memory impairment using a two-sample two-way Mendelian randomization (MR) approach. Methods The data for this study was sourced from the genome-wide association studies database and analyzed using a two-sample two-way MR method. In the forward study, the exposure factor was heart failure, and the outcome was memory loss. In the reverse study, the exposure factor was memory loss, and the outcome was heart failure. The instrumental variables were selected, and the causal relationship between heart failure and memory impairment was mainly analyzed using the inverse variance weighted method (IVW). At the same time, MR Egger regression, weighted mode, weighted median estimator, and simple mode were used to supplement the IVW analysis results. Cochran’s Q test was used to assess statistical heterogeneity among single nucleotide polymorphisms (SNPs), the intercept term of MR Egger regression was used to evaluate the presence of horizontal pleiotropy among SNPs, and the leave one method was used to evaluate the impact of individual SNPs on IVW analysis results. To avoid reverse causality, memory loss was identified as the exposure factor and heart failure as the outcome event, and reverse MR analysis was conducted. Results A total of 9 SNPs strongly associated with heart failure. The IVW analysis results [β=−0.81, odds ratio (OR)=0.45, 95% confidence interval (CI) (0.27, 0.73), P=0.0015] showed a negative causal relationship between heart failure and memory impairment. The results of weighted median estimator [β=−0.92, OR=0.40, 95%CI (0.21, 0.77), P=0.0059] and weighted mode [β=−1.16, OR=0.31, 95%CI (0.12, 0.83), P=0.047] showed a negative causal relationship between heart failure and memory impairment. Although MR Egger regression [β=−1.19, OR=0.30, 95%CI (0.08, 1.21), P=0.14] and simple mode [β=−0.32, OR=0.72, 95%CI (0.26, 2.01), P=0.55] analysis showed that heart failure did not increase the risk of memory loss. Cochran’s Q test and prompt yielded robust and non-heterogeneous results (P=0.890), while the intercept assessment of MR Egger regression indicated stable results without horizontal pleiotropy (P=0.578). Reverse MR analysis revealed that there was no causal relationship between exposure factor memory impairment and outcome heart failure [β=3.71×10−3, OR=1.00, 95%CI (0.96, 1.03), P=0.85]. Conclusions There is a negative correlation between genetic prediction of heart failure and the risk of memory loss, which is inconsistent with clinical observations and previous research conclusions. Observational associations may be overestimated or misled, which is also one of the core values of MR research.