Objective To investigate the causal relationship between resistin and multiple myeloma (MM). Methods A two-sample Mendelian randomization analysis was conducted using genetic variants (SNPs) associated with resistin as instrumental variables and MM genome-wide association study (GWAS) data as the outcome event. Five analysis methods, including inverse-variance weighted (IVW), MR-Egger, weighted median, weighted model, and simple model were used to assess the causal impact of resistin on the risk of MM. Results None of the five analysis methods showed a causal relationship between resistin and multiple myeloma (P>0.05). Sensitivity analysis indicated consistent and robust results, with no evidence of horizontal pleiotropy, heterogeneity, outliers, or individual SNPs influencing the findings. Conclusion This Mendelian randomization study provides no support for a causal relationship between resistin and the risk of multiple myeloma.
ObjectiveTo investigate the causal relationship between gastroesophageal reflux disease (GERD) and obstructive sleep apnea (OSA) with its typical symptoms (snoring and daytime sleepiness) by using Mendelian randomization (MR). MethodsThe inverse-variance weighted method was used as the main analysis method to assess the causal effect. Sensitivity and pleiotropy analyses were carried out using leave-one-out and MR-Egger analysis, and then heterogeneity tests were conducted. ResultsIn the MR analysis, genetically predicted GERD was associated with a greater risk of OSA (IVW: OR=1.528, 95%CI 1.374 to 1.699, P=5.315E?15). Additional MR results were consistent with the IVW results, and no pleiotropy or heterogeneity was found. We also discovered a significant causal relationship between GRED and snoring (IVW: OR=0.959, 95%CI 0.949 to 0.969, P=1.507E?15), and daytime sleepiness (IVW: OR=1.024, 95%CI 1.021 to 1.036, P=4.580E?5), with no evidence of pleiotropy. ConclusionThe MR study supports a causal effect between GERD and OSA with its typical symptoms (daytime sleepiness and snoring).
Objective To explore the causal association between obstructive sleep apnea (OSA) and venous thromboembolism (VTE). Methods Using the summary statistical data from the FinnGen biological sample library and IEU OpenGWAS database, the relationship between OSA and VTE, including deep vein thrombosis (DVT) and pulmonary embolism, was explored through Mendelian randomization (MR) method, with inverse variance weighted (IVW) as the main analysis method. Results The results of univariate MR analysis using IVW method showed that OSA was associated with VTE and pulmonary embolism (P<0.05), with odds ratios and 95% confidence intervals of 1.204 (1.067, 1.351) and 1.352 (1.179, 1.544), respectively. There was no correlation with DVT (P>0.05). Multivariate MR analysis showed that after adjustment for confounding factors (smoking, diabetes, obesity and cancer), OSA was associated with VTE, DVT and pulmonary embolism (P<0.05), with odds ratios and 95% confidence intervals of 1.168 (1.053, 1.322), 1.247 (1.064, 1.491) and 1.158 (1.021, 1.326), respectively. Conclusion OSA increases the risk of VTE, DVT, and pulmonary embolism.
Objective To explore the correlation between physical activity, sleep and aging using a two-sample Mendelian randomization (MR) method. Methods The data through genome-wide association studies was summarized. The single nucleotide polymorphisms (SNPs) related to physical activity and sleep as instrumental variables was selected. The inverse variance weighting method was used for the main analyses, complemented by the weighted median method and MR Egger regression, and then sensitivity analyses were carried out in terms of multiplicity, heterogeneity and leave-one-out method. Finally, multivariate Mendelian methods were applied to eliminate confounders and find mediators. Results A total of two types of physical activity (strong physical activity, physical inactivity) and three sleep conditions (daytime naps, short sleep duration, adequate sleep duration) were found to have a causal relationship with frailty index (P<0.05), while physical inactivity was found to have a causal relationship with telomere length (P<0.05). A total of 167 SNPs were included in the analysis. Strong physical activity [correlation coefficient (β)=?1.26, 95% confidence interval (CI) (?1.60, ?0.96), P<0.0001], adequate sleep duration [β=?0.17, 95%CI (?0.26, ?0.09), P<0.001] were negatively correlated with the frailty index. Physical inactivity [β=1.47, 95%CI (0.85, 2.08), P<0.001], daytime naps [β=0.25, 95%CI (0.12, 0.39), P=0.0002], and short sleep duration [β=0.20, 95%CI (0.13, 0.27), P<0.0001] were positively associated with frailty index. Physical inactivity [β=?0.38, 95%CI (?0.69, ?0.07), P=0.02] was negatively correlated with telomere length. Percentage body fat, body fat mass, waist circumference, body weight and body mass index partially mediated 25.52%, 23.52%, 10.08%, 17.6% and 10.08% of the effect between daytime naps and frailty index, respectively. Conclusion There is a causal relationship between physical activity, sleep, and aging.
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 DNA copy number and the risk of Alzheimer disease (AD) using Mendelian randomization (MR) methods, as well as to investigate the potential mediating effects of immune cells. Methods The data related to 731 immune cell types, DNA copy number and AD from the Genome-Wide Association Study database were collected. A bidirectional MR analysis was conducted to explore the causal relationship between DNA copy number and AD, primarily using the inverse-variance weighted method and MR-Egger method. Additionally, a two-step mediation analysis was performed to identify potential mediating immune cells. Results A total of 134 single-nucleotide polymorphisms were included for bidirectional MR analysis. The MR methods results showed a negative causal relationship between DNA copy number and the risk of AD (P<0.05), while the reverse analysis showed no statistical significance. Sensitivity analysis confirmed the robustness of these results. The mediation analysis indicated that the immune cell phenotype (HVEM on CD45RA-CD4+) partially mediated the causal relationship between DNA copy numbers and the risk of AD, with a mediation effect proportion of 4.6%. Conclusion An increase in DNA copy numbers may reduce the risk of AD, and immune cells partially mediate this causal relationship.
Objective To analyze the causal relationship between cerebrospinal fluid (CSF) metabolites and tic disorder (TD) based on two-sample Mendelian randomization (MR). Methods CSF metabolites data from humans were downloaded from genome-wide association study databases, and CSF metabolites were selected as exposure factors. single nucleotide polymorphisms (SNPs) strongly associated with the exposure factors and independent of each other were selected as instrumental variables. The TD dataset from the Finngen database was downloaded, including 365 cases of TD and 411 816 controls. Analysis was conducted using inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode. Sensitivity analysis was conducted using leave-one-out, and multiple-effects testing was conducted using MR-Egger and MR-PRESSO. Heterogeneity was detected using Cochran’s Q. Results A total of 9 CSF metabolites were found to have a causal relationship with the occurrence and development of TD (P<0.05), with a total of 394 SNPs included in the analysis. Inverse variance weighting results showed that N-acetylneuraminic acid [odds ratio (OR)=2.715, 95% confidence interval (CI) (1.102, 6.961), P=0.030], γ-glutamylglutamine [OR=1.402, 95%CI (1.053, 1.868), P=0.021], lysine [OR=2.816, 95%CI (1.084, 7.319), P=0.034] could increase the risk of TD. Cysteinylglycine disulfide [OR=0.437, 95%CI (0.216, 0.885), P=0.021], propionylcarnitine [OR=0.762, 95%CI (0.616, 0.941), P=0.012], pantothenate [OR=0.706, 95%CI (0.523, 0.952), P=0.023], gulareic acid [OR=0.758, 95%CI (0.579, 0.992), P=0.044], and cysteine-glycine [OR=0.799, 95%CI (0.684, 0.934), P=0.005] could reduce the risk of TD. The results of leave-one-out sensitivity analysis were stable, and no horizontal pleiotropy or heterogeneity was observed. Conclusions N-acetylneuraminic acid, γ-glutamylglutamine, and lysine can increase the risk of TD, but cysteinylglycine disulfide, propionylcarnitine, pantothenate, gulagic acid and cysteine-glycine can reduce the risk of TD. However, the mechanism of their effects on TD still needs to be further explored.
Objective To analyze the potential causal relationship between sunscreen/ultraviolet protection and the risk of non-Hodgkin lymphoma using a two sample Mendelian randomization (MR) study method. Methods The summary data of genome-wide association study was used to select three types of non-Hodgkin lymphoma, namely diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, T/NK cell lymphoma, and sunscreen/ultraviolet protection highly correlated genetic loci, namely single nucleotide polymorphism (SNP), as instrumental variables. The reverse variance weighting method was used as the main method for MR analysis, MR Egger and MR-PRESO were used to detect level pleiotropy, and leave-one-out method was used for sensitivity analysis to ensure the robustness of the results. Results A total of 132 SNPs were included in the analysis. The results of the inverse variance weighted analysis showed that sunscreen/ultraviolet protection increased the incidence of DLBCL [odds ratio=2.439, 95% confidence interval (1.109, 5.362), P=0.027]. The heterogeneity test results showed that there was no heterogeneity in the causal relationship between sunscreen/ultraviolet protection and DLBCL (P>0.05). The results of the horizontal pleiotropy test showed that SNP did not exhibit horizontal pleiotropy (P>0.05). The leave-one-out method showed that no SNP with a significant impact on the results was found. There was no causal relationship between sunscreen/ultraviolet protection and follicular lymphoma and T/NK cell lymphoma. Conclusion There is a positive causal relationship between sunscreen/ultraviolet protection and the incidence of DLBCL.
Objective To explore the causal relationship between gut microbiota and urinary tract infections (UTI) using data from genome-wide association studies. Methods The gut microbiota data were sourced from the MiBioGen consortium, comprising genetic variables from 18 340 individuals. UTI data (ieu-b-5.65) were derived from the UK Biobank. Six methods including inverse variance weighted (IVW), Mendelian randomization (MR)-Egger, maximum likelihood, simple mode, weighted mode, and weighted median were employed for two-sample MR analysis on these datasets. Additionally, MR-PRESSO was used to detect and correct for heterogeneity and outliers in the analysis. Cochran’s Q test and leave-one-out analysis were applied to assess potential heterogeneity and multiple effects. Furthermore, reverse MR analysis was conducted to investigate causal relationships between UTI and gut microbiota. Results According to IVW method analysis results, bacterial genera Eggerthella (OR=1.08, 95%CI 1.01 to 1.16, P=0.034) and Ruminococcaceae (UCG005) (OR=1.10, 95%CI 1.01 to 1.20, P=0.022) were found to increase the risk of UTI, while Defluviitaleaceae (UCG011) (OR=0.90, 95%CI 0.82 to 0.99, P=0.022) appeared to decrease it. Reverse MR analysis did not reveal a significant effect of UTI on these three bacterial genera. Our study found no evidence of heterogeneity or pleiotropy based on the results of Cochran’s Q test, MR-Egger, and MR-PRESSO global test. Conclusion In this MR study, we demonstrate a causal association between Eggerthella, Ruminococcaceae, Defluvitalaceae and the risk of urinary tract infections.
ObjectiveTo investigate the bidirectional causal relationship between metabolic syndrome (MS) and inflammatory bowel disease (IBD) using Mendelian randomization (MR). MethodsWe extracted genetic variants with strong correlations from genome-wide association study data on MS as instrumental variables. Inverse variance weighting, MR-Egger regression methods, and weighted median methods were used to estimate the causal effect of MS and risk of developing IBD. ResultsInverse variance weighting found that genetically predicted MS was associated with an increased risk of developing IBD overall (OR=1.113, 95%CI 1.020 to 1.216, P=0.017) and Crohn's disease (OR=1.195, 95%CI 1.072 to 1.333, P=0.001). And inverse MR analysis found ulcerative colitis was associated with a reduced risk of developing MS (OR=0.969, 95%CI 0.948 to 0.991, P=0.005). ConclusionThe results based on MR analysis suggest that genetically predicted MS is associated with the risk of IBD as a whole and Crohn's disease and ulcerative colitis are associated with a reduced risk of developing MS.
