Objective To analyze whether there is a causal association between psoriasis and Alzheimer disease (AD) by a two-sample two-way Mendelian randomization (MR) method. Methods In the forward study, the single nucleotide polymorphisms (SNPs) associated with psoriasis were obtained from the comprehensive statistical data of the genome-wide association study database as the instrumental variables, and AD as the outcome; in the reverse study, the SNPs associated with AD were taken as instrumental variables, and psoriasis as the outcome. Using two-sample two-way MR analysis, the odds ratio (OR) value and 95% confidence interval (CI) of regression models, namely inverse variance weighted (IVW) method, MR-Egger regression method, weighted median method, simple pattern method, and weighted pattern method, were used to evaluate the causal relationship between psoriasis and AD. Cochran’s Q test was used to assess the heterogeneity of genetic instrumental variables, MR-Egger intercept method was used to test the horizontal pleiotropy of the assessment, “leave-one-out” method was used to assess the sensitivity of a SNP to the effect of causality, and the symmetry of funnel plot was observed to assess bias. Results A total of 19 SNPs associated with psoriasis were included as instrumental variables in the forward study. The IVW analysis of the forward study showed that there was a causal correlation between psoriasis and AD [OR=1.032, 95%CI (1.014, 1.051), P<0.001], and MR-Egger regression method [OR=1.042, 95%CI (1.012, 1.073), P=0.013], weighted median [OR=1.048, 95%CI (1.023, 1.074), P<0.001], and weighted model [OR=1.046, 95%CI (1.020, 1.073), P=0.002] all supported this result. Heterogeneity test (IVW result: Q=13.752, P=0.745; MR-Egger regression result: Q=13.134, P=0.727), MR-Egger intercept method (Egger intercept=–0.004, P=0.442), the results of “leave-one-out” method and funnel plot showed that the results of MR analysis were reliable. A total of 127 AD-related SNPs were included as instrumental variables in the reverse study. In reverse research, there was no evidence to support the AD could increase the risk of psoriasis (P>0.05). Heterogeneity test (IVW result: Q=232.496, P<0.001; MR-Egger regression result: Q=232.119, P<0.001) suggested heterogeneity, but MR-Egger intercept method (Egger intercept=0.003, P=0.652), the results of “leave-one-out” method and funnel plot showed that the results of MR analysis were reliable. Conclusion There is a causal association between psoriasis and AD, and psoriasis may increase the risk of AD.
Lung cancer is a major cause of cancer mortality worldwide, but the risk factors contributing to its development are not yet fully elucidated. Deepening the understanding of the risk factors and potential complications associated with lung cancer is of significant importance for the prevention and treatment of this disease. Traditional observational clinical studies and randomized controlled trials, due to the influence of various factors, render the process of causal inference more complex and may introduce biases into the results. Compared to the traditional methods, Mendelian randomization (MR) has attracted an increasing amount of attention in lung cancer research, due to its simplicity of operation and effective control of confounding factors and reverse causality biases. This paper employs bibliometric methods to analyze the published MR studies related to lung cancer, and further summarizes and discusses the content of these studies. The findings indicate that traditional risk factors, such as lifestyle habits, nutrition, obesity, socioeconomic factors, environmental pollution, and inflammatory biomarkers, have been substantiated within the context of MR studies. Additionally, MR studies support the existence of causal relationships between lung cancer and certain gut microbiota, medications, and other systemic diseases. Despite the inherent limitations of MR studies, they nonetheless hold significant value in enhancing our comprehension of the etiology of lung cancer and in identifying potential therapeutic interventions.
Objective To explore the causal association between radiation exposure and risk of head and neck cancer using Mendelian randomization (MR) method. Methods Genome-wide association studies of radiation exposure and head and neck cancer in the public database IEU OpenGWAS were identified, and single nucleotide polymorphisms (SNPs) were screened as instrumental variables. Two-sample MR analyses were performed using random-effect inverse variance weighted (IVW), fixed-effect IVW, weighted median, and MR-Egger methods to assess the causal association between radiation exposure and risk of head and neck cancer. Outliers were tested using the MR-PRESSO method, and heterogeneity was assessed using the Cochran Q test. MR-Egger regression intercept was utilized to detect gene-level pleiotropy, and a leave-one-out sensitivity analysis was conducted to evaluate the robustness of the study results. Results96 valid SNPs were included as instrumental variables. The analysis results of random-effect IVW method, fixed-effect IVW method, and weighted median method all showed that radiation exposure was associated with an increased risk of head and neck cancer [odds ratio and 95% confidence interval: 1.139 (1.065, 1.218), 1.139 (1.068, 1.215), and 1.141 (1.039, 1.253); P<0.05]. Heterogeneity testing did not reveal significant heterogeneity, MR-Egger regression analysis did not find gene level pleiotropy, and the leave-one-out method did not find a single SNP significantly affecting the overall estimation results. Conclusion Radiation exposure increases the risk of head and neck cancer, but this conclusion still needs further validation in more high-quality, large sample studies.
ObjectiveTo analyze the causal relationship between the intake of cheese or tea and the risk of gastroesophageal reflux disease (GERD). MethodsUsing a two-sample Mendelian randomization approach, single nucleotide polymorphisms (SNPs) associated with milk or tea intake were used as instrumental variables. The causal effect of milk or tea intake on the risk of GERD was investigated using the MR Egger method, the weighted median method, the inverse-variance weighted (IVW) random-effects model, and the IVW fixed-effects model. Multivariable analysis was conducted using the MR Egger method, and leave-one-out sensitivity analysis was performed to validate the reliability of the data. ResultsCheese intake could reduce the occurrence of GERD [IVW random-effects model β=–1.010, 95%CI (0.265, 0.502), P<0.05], while tea intake could lead to the occurrence of GERD [IVW random-effects model β=0.288, 95%CI (1.062, 1.673), P<0.05]. ConclusionCheese intake may have a positive causal relationship with reducing the risk of GERD occurrence, while tea intake may have a positive causal relationship with increasing the risk of GERD occurrence.
ObjectiveExploring the potential causal effects and directions of insulin resistance (IR) and chronic airway inflammatory diseases, including asthma and chronic obstructive pulmonary disease (COPD), through two sample Mendelian randomization (MR). MethodsA total of 53 validated single nucleotide polymorphisms (SNPs) associated with IR were selected as instrumental variables. The inverse variance-weighted (IVW) method was used to model the causal association, and sensitivity analyses through leave-one-out analysis and pleiotropy testing were conducted to assess the relationship between IR and asthma and COPD. ResultsMR analysis revealed no significant causal effect of IR on asthma (IVW: OR=1.067, 95%CI 0.871 to 1.306, P=0.531) or COPD (IVW: OR=0.906, 95%CI 0.686 to 1.196, P=0.557). The results were consistent across sensitivity analyses and multiple pleiotropy tests, with no evidence of horizontal pleiotropy detected. ConclusionNo causal association was found between IR and the development of asthma or COPD. The relationship between these conditions may be influenced indirectly through complex interactions between metabolic and inflammatory pathways affecting disease progression.
Objective To analyze the causal relationship between educational attainment and the risk of systemic lupus erythematosus (SLE). Methods Based on the data from publicly available genome-wide association studies, we employed single nucleotide polymorphisms (SNPs) strongly associated with educational attainment as instrumental variables. Two-sample Mendelian randomization analysis was used to investigate the causal relationship between educational attainment and SLE. The primary analysis method used was the inverse variance weighted with multiplicative random effects. Validation methods included inverse variance weighted with fixed effects and MR-Egger methods. Additionally, sensitivity analysis was conducted using the leave-one-out approach. Results Finally, 433 SNPs were included. The inverse variance weighted with multiplicative random effects analysis indicated no causal effect of educational attainment on the risk of SLE [odds ratio =1.111, 95% confidence interval (0.813, 1.518), P=0.509]. Similarly, the other two methods did not find any evidence of a causal relationship (P>0.05); however, significant heterogeneity was observed. The MR-Egger regression analysis provided no evidence of horizontal pleiotropy among the included instrumental variables (P>0.05). The leave-one-out approach did not identify any individual SNP that had a significant impact on the overall effect estimate. ConclusionIn conclusion, this study does not support a causal effect of educational attainment on the risk of SLE.
Objective To explore the potential causal relationship between thyroid dysfunction and osteoporosis (OP) through bidirectional two-sample Mendelian randomization (MR) analysis to provide genetic evidence for the risk association between thyroid dysfunction and OP, and provide reference for early prevention and treatment of OP. Methods Causal relationships were estimated based on data from genome-wide association studies for hypothyroidism (n=410141), hyperthyroidism (n=460499), Hashimoto thyroiditis (n=395640), and OP (n=212778). The inverse variance weighted method was used as the main analysis method, and the other four methods were used as the supplementary analysis methods to evaluate the causal effect of thyroid dysfunction and OP. Results The results of inverse variance weighted method showed that hypothyroidism [odds ratio (OR)=1.097, 95% confidence interval (CI) (1.017, 1.183), P=0.017], hyperthyroidism [OR=1.089, 95%CI (1.000, 1.186), P=0.049] and Hashimoto thyroiditis [OR=1.190, 95%CI (1.054, 1.343), P=0.005] were positively correlated with the causal effect of OP. The results of reverse MR analysis did not support that OP would increase the risk of hypothyroidism, hyperthyroidism or Hashimoto thyroiditis (P>0.05). In the bidirectional MR analyses, there was no heterogeneity in Cochran Q detection, MR-Egger intercept test results showed that there was no horizontal pleotropy, and the leave-one-out method analysis results showed that the MR analysis results were reliable. Conclusion Hypothyroidism, hyperthyroidism, and Hashimoto thyroiditis increase the risk of OP, while OP is not found to increase the risk of thyroid dysfunction in reverse studies.
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.
ObjectiveTo conduct a Mendelian randomization (MR) analysis to elucidate the potential causal relationship between sarcopenia (SA) and knee osteoarthritis (KOA). MethodsThree SA-related traits were selected as exposure factors from the summary data of the genome-wide association studies database (IEU GWAS). KOA and hospital-diagnosed osteoarthritis of the knee (osteoarthritis of the knee hospital diagnosed) were chosen as outcome factors. The inverse variance-weighted (IVW) method was employed as the primary analytical approach to evaluate the causal relationship between SA and KOA. Heterogeneity tests, sensitivity analyses, and pleiotropy analyses were conducted to validate the reliability of the results. ResultsThe MR results indicated a substantial causal relationship between genetically predicted appendicular muscle mass (OR=1.079, 95%CI 1.015 to 1.147, P=0.015 5), walking speed (OR=0.157, 95%CI 0.101 to 0.248, P<0.001). No significant causal relationship was found between grip strength and KOA (OR=1.318, 95%CI 0.933 to 1.859, P=0.116 6), and the sensitivity analysis results did not exhibit horizontal pleiotropy. ConclusionSA may have a causal relationship with KOA, and appendicular muscle mass and walking speed may be risk factors for the occurrence and development of KOA.
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.