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 evaluate the association between vitamin D levels and polycystic ovarian syndrome (PCOS) by Mendelian randomization (MR) analysis, and assess the role of obesity in this association. Methods Public genome-wide association studies were used to obtain single nucleotide polymorphism (SNP) data of exposure and outcome. Inverse variance weighting (IVW) was used as the main analysis method to analyze the causal relationship between vitamin D level (including total vitamin D level, serum 25-hydroxyvitamin D level) and vitamin D-binding protein level and polycystic ovary syndrome. In addition, multivariate MR method was used to explore the influence of obesity. Results IVW method showed that 25-hydroxyvitamin D was a protective factor for PCOS (OR=0.185, 95%CI 0.058 to 0.585, P=0.004). There was no interference of heterogeneity or horizontal pleiotropy among the data, and the data tended to be stable in general. The remaining total vitamin D levels and vitamin D-binding protein levels did not show an association with PCOS at the genetic level. MVMR analysis adjusted for obesity and BMI in adolescents showed that 25-hydroxyvitamin D was still negatively associated with the risk of PCOS. Conclusion By bidirectional Mendelian randomization analysis, serum 25-hydroxyvitamin D is identified as a protective factor for PCOS, and the increase of serum 25-hydroxyvitamin D level can reduce the risk of PCOS. Obesity does not affect the causal relationship between serum 25-hydroxyvitamin D and PCOS at the genetic level.
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.
Objective To analyze the relationship between neuroticism and gastroesophageal reflux disease (GERD) using the Mendelian randomization (MR) method. Methods Exposure and outcome data were downloaded from the Integrative Epidemiology Unit (IEU) database in August 2023, including summary statistics from genome-wide association studies (GWAS) for neuroticism (n=374 323) and GERD (n=602 604). MR was conducted using the weighted median method, MR-Egger method, inverse variance weighted method, weighted mode method, and simple mode method. The causal relationship between the two was assessed using odds ratio (OR), and sensitivity analyses were performed to ensure the accuracy of the results. ResultsNeuroticism was associated with an increased risk of GERD [OR=1.229, 95%CI (1.186, 1.274), P<0.001]. Similarly, GERD was associated with an increased risk of neuroticism [OR=1.786, 95%CI (1.623, 1.965), P<0.001]. Conclusion There is a bidirectional causal relationship between neuroticism and gastroesophageal reflux disease.
ObjectiveTo investigate whether there is a causal relationship between the intake of milk or coffee and the risk of non-alcoholic fatty liver disease (NAFLD). MethodsUsing a two-sample Mendelian randomization approach, single nucleotide polymorphisms (SNPs) associated with milk or coffee intake were used as instrumental variables, and genome-wide association study data on NAFLD were used as the outcome event. Inverse-variance weighted (IVW) and MR-Egger methods were employed to investigate the causal effect of milk or coffee intake on the risk of NAFLD. ResultsBoth analyses indicated no causal association between milk or coffee intake and the risk of NAFLD (P>0.05). Sensitivity analysis indicated the robustness of the main findings, with no outliers, heterogeneity, horizontal pleiotropy, or significant influence of individual SNPs. ConclusionThis study does not support a causal relationship between the intake of milk or coffee and the risk of NAFLD.
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.
Mendelian randomization (MR) studies use genetic variants as instrumental variables to explore the effects of exposures on health outcomes. STROBE-MR (strengthening the reporting of observational studies in epidemiology using Mendelian randomization) assists authors in reporting their MR studies clearly and transparently, and helpfully to improve the quality of MR. This paper interpreted the STROBE-MR, aiming to help Chinese scholars better understand, disseminate, and apply it.
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 explore the relationship between the gut microbiome (GM) and psoriasis using a two-sample two-way Mendelian randomization (MR) approach. Methods The forward analysis uses the gut microbiota as the exposure factor, and its genetic data are derived from the genome-wide association study dataset published by the MiBioGen consortium. Psoriasis was used as the outcome variable, and its genetic data were obtained from the UK Biobank. The reverse MR analysis, on the other hand, took psoriasis as the exposure and the specific gut microbiota taxonomic units identified in the forward analysis as the outcome variable. MR analysis was conducted using maximum likelihood, MR Egger regression, weighted median, inverse variance weighting (IVW), and weighted models to study the causal relationship between the gut microbiota and psoriasis. Then, sensitivity analyses including horizontal pleiotropy test, Cochran’s Q test, and leave-one-out analysis were used to evaluate the reliability of the results. Results A total of 51 single nucleotide polymorphisms from 5 fungi were included in the forward study. The forward IVW analysis results showed that, the class Mollicutes [odds ratio (OR)=1.003, 95% confidence interval (CI) (1.001, 1.006), P=0.004], genus Lachnospiraceae FCS020 group [OR=1.003, 95%CI (1.000, 1.006), P=0.041], and phylum Tenericutes [OR=1.003, 95%CI (1.001, 1.006), P=0.004] were causally associated with an increased risk of psoriasis. The family Victivallaceae [OR=0.998, 95%CI (0.997, 1.000), P=0.005] and order Pasteurellales [OR=0.998, 95%CI (0.996, 1.000), P=0.047] were also linked to a decreased risk of psoriasis. The results of the sensitivity analysis were robust. There was no evidence of a reverse causal relationship from psoriasis to the identified bacterial taxa found in the results of reverse MR analysis results. Conclusions The abundance of three species, class Mollicutes, genus Lachnospiraceae and phylum Tenericutes, may increase the risk of psoriasis. The abundance of two species, family Victivallaceae and order Pasteurellales may reduce the risk of psoriasis. These results provide new directions for the prevention and treatment of psoriasis in the future, but further research is needed to explore how the aforementioned microbiome affects the progression of psoriasis.
ObjectiveTo explore the causal association between venous thromboembolism (VTE) and cardiovascular disease (CVD) risks using a two-sample bidirectional Mendelian randomization (MR) study. MethodsThe single-nucleotide polymorphism (SNP) data associated with VTE and CVD from genome-wide association studies were obtained as instrumental variables. Inverse variance weighted (IVW) was used as the main MR method and other methods were used as supplementary methods. Cochran's Q test, the intercept term of MR-Egger, and MR-PRESSO were used to assess pleiotropy and heterogeneity to ensure the robustness of the results. ResultsThe IVW method suggested a causal association between VTE and atrial fibrillation (OR=1.033, 95%CI 1.009 to 1.058, P=0.008), but no association was identified between VTE and coronary artery disease (OR=0.994, 95%CI 0.974 to 1.023, P = 0.551), heart failure (OR=1.021, 95%CI 0.992 to 1.050, P=0.159) and myocardial infarction (OR=1.012, 95%CI 0.971 to 1.055, P=0.568). The results of Cochran's Q test showed that there was no heterogeneity in the MR analyses of VTE and CVD. The MR-Egger intercept analysis and the MR-PRESSO global testing did not detect potential horizontal pleiotropy, and the results were robust. Reverse MR analysis was used to verify the presence of reverse causal associations. The reverse MR analysis demonstrated that reverse causal associations between VTE and CVD were not evidenced. ConclusionThe results of the MR study demonstrated a causal association between VTE and atrial fibrillation, but not with coronary artery disease, heart failure or myocardial infarction.