Major depressive disorder and the risk of irritable bowel syndrome: A Mendelian randomization study
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ABSTRACT:
SUBMITTER: Zhu R
PROVIDER: S-EPMC10912794 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Project description:There is some evidence of a link between fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet and irritable bowel syndrome (IBS). However, few studies have analyzed the relationship between specific dietary intakes and IBS using Mendelian randomization (MR). Exposure and outcome datasets were sourced from the IEU Open GWAS project. Genetic variants significantly associated with 28 dietary intakes at a genome-wide level were selected as instrumental variables. Summary statistics for the target outcome of IBS were obtained with a sample of 187,028 European individuals (4605 cases, 182,423 controls). Univariable and multivariable MR analyses were conducted to estimate the overall and independent MR associations after adjustment for genetic liability to intestinal flora. Genetic predispositions to six of 28 dietary intakes were associated with a decreased risk of IBS, including dried fruit, beef, cereal, lobster/crab, cereal, feta, and coffee, while cherry and poultry intake were associated with an increased risk of IBS. Three of eight associations persisted after adjusting for genetically predicted intestinal flora, and multivariable MR analysis identified that salad/raw vegetable intake was associated with a decreased risk of IBS. Twenty of 28 dietary intakes did not remain significantly associated after adjustment for intestinal flora. This study provides MR evidence supporting causal associations between FODMAP dietary intakes and IBS.
| S-EPMC11833296 | biostudies-literature
Project description:Background: Whether a gluten-free diet (GFD) is a cause of irritable bowel syndrome (IBS) remains controversial. We aim at exploring the causal relationship between gluten intake and IBS within Mendelian randomization (MR) design. Methods: We conducted a two-sample MR and selected single-nucleotide polymorphisms (SNPs) associated with GFD as instrumental variables (IVs). SNPs and genetic associations with GFD and IBS were obtained from the latest genome-wide association studies (GWAS) in Europeans (GFD: cases: 1,376; controls: 63,573; IBS: cases:1,121; controls: 360,073). We performed inverse variance weighting (IVW) as the primary method with several sensitivity analyses like MR-Egger and MR-PRESSO for quality control. The above analyses were re-run using another large dataset of IBS, as well as changing the p-value threshold when screening IVs, to verify the stability of the results. Results: The final estimate indicated significant causal association [per one copy of effect allele predicted log odds ratio (OR) change in GFD intake: OR = 0.97, 95% confidence interval (CI) 0.96 to 0.99, p < 0.01] without heterogeneity statistically (Q = 2.48, p = 0.78) nor horizontal pleiotropy biasing the causality (p = 0.92). Consistent results were found in validation analyses. Results of MR Steiger directionality test indicated the accuracy of our estimate of the causal direction (Steiger p < 0.001). Conclusion: GFD might be a protective factor of IBS. Therefore, we suggest taking a diet of lower gluten intake into account in IBS prevention and clinical practice.
| S-EPMC8660079 | biostudies-literature
Project description:ObjectiveTo explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer disease (AD).MethodsWe conducted bidirectional 2-sample Mendelian randomization analyses. Genetic associations were obtained from the largest genome-wide association studies currently available in UK Biobank (n = 446,118), Psychiatric Genomics Consortium (n = 18,759), and International Genomics of Alzheimer's Project (n = 63,926). We used the inverse variance-weighted Mendelian randomization method to estimate causal effects and weighted median and Mendelian randomization-Egger for sensitivity analyses to test for pleiotropic effects.ResultsWe found that higher risk of AD was significantly associated with being a "morning person" (odds ratio [OR] 1.01, p = 0.001), shorter sleep duration (self-reported: β = -0.006, p = 1.9 × 10-4; accelerometer based: β = -0.015, p = 6.9 × 10-5), less likely to report long sleep (β = -0.003, p = 7.3 × 10-7), earlier timing of the least active 5 hours (β = -0.024, p = 1.7 × 10-13), and a smaller number of sleep episodes (β = -0.025, p = 5.7 × 10-14) after adjustment for multiple comparisons. We also found that higher risk of AD was associated with lower risk of insomnia (OR 0.99, p = 7 × 10-13). However, we did not find evidence that these abnormal sleep patterns were causally related to AD or for a significant causal relationship between MDD and risk of AD.ConclusionWe found that AD may causally influence sleep patterns. However, we did not find evidence supporting a causal role of disturbed sleep patterns for AD or evidence for a causal relationship between MDD and AD.
| S-EPMC7682841 | biostudies-literature
Project description:Associations between leisure sedentary behavior (especially leisure screen time, LST) and irritable bowel syndrome (IBS) have been reported, but causality is unclear. Here, the two-sample Mendelian randomization was performed to investigate the causal association between LST and IBS. Two recently published genome-wide association studies (GWASs) including a total of 1,190,502 people from Europe were used as our data source. Inverse variance weighting (OR = 1.120, 95% CI 1.029-1.219) and weighted median (OR = 1.112, 95% CI 1.000-1.236) analyses revealed a causal effect between LST and IBS. There was no evidence of pleiotropy in the sensitive analysis (MR-Egger, p = 0.139). After removing potentially confounding single nucleotide polymorphisms (SNPs), similar results were found using inverse variance weighting (OR = 1.131, 95% CI 1.025-1.248) and weighted median (OR = 1.151, 95% CI 1.020-1.299), as well as in the validation analyses using inverse variance weighting (OR = 1.287, 95% CI 0.996-1.662). This study provided support for a possible causal relationship between leisure screen time and IBS.
| S-EPMC10425325 | biostudies-literature
Project description:BackgroundIrritable bowel syndrome (IBS) is one of the most common functional bowel disorders and dysmetabolism plays an important role in the pathogenesis of disease. Nevertheless, there remains a lack of information regarding the causal relationship between circulating metabolites and IBS. A two-sample Mendelian randomization (MR) analysis was conducted in order to evaluate the causal relationship between genetically proxied 486 blood metabolites and IBS.MethodsA two-sample MR analysis was implemented to assess the causality of blood metabolites on IBS. The study utilized a genome-wide association study (GWAS) to examine 486 metabolites as the exposure variable while employing a GWAS study with 486,601 individuals of European descent as the outcome variable. The inverse-variance weighted (IVW) method was used to estimate the causal relationship of metabolites on IBS, while several methods were performed to eliminate the pleiotropy and heterogeneity. Another GWAS data was used for replication and meta-analysis. In addition, reverse MR and linkage disequilibrium score regression (LDSC) were employed for additional assessment. Multivariable MR analysis was conducted in order to evaluate the direct impact of metabolites on IBS.ResultsThree known and two unknown metabolites were identified as being associated with the development of IBS. Higher levels of butyryl carnitine (OR(95%CI):1.10(1.02-1.18),p = 0.009) and tetradecanedioate (OR(95%CI):1.13(1.04-1.23),p = 0.003)increased susceptibility of IBS and higher levels of stearate(18:0)(OR(95%CI):0.72(0.58-0.89),p = 0.003) decreased susceptibility of IBS.ConclusionThe metabolites implicated in the pathogenesis of IBS possess potential as biomarkers and hold promise for elucidating the underlying biological mechanisms of this condition.
| S-EPMC10990233 | biostudies-literature
Project description:BackgroundThe association between psychiatric disorders and dentofacial deformities has attracted widespread attention. However, their relationship is currently unclear and controversial.MethodsA two-sample bidirectional MR analysis was performed to study the causal relationship between dentofacial deformity and eight psychiatric disorders, including major depressive disorder, panic disorder, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, Alzheimer's disease, autism spectrum disorder, and neuroticism. Inverse variance weighted, weighted median, MR-Egger regression, weighted mode four methods, and further sensitivity analyses were conducted.ResultsThe major depressive disorder affected dentofacial deformity, with an OR = 1.387 (95% CI = 1.181-1.629, P = 6.77×10-5). No other psychiatric disorders were found to be associated with dentofacial deformity. In turn, dentofacial deformity were associated with neuroticism, with an OR = 1.050 (95% CI = 1.008-1.093, P = 0.018). And there was no evidence that dentofacial deformity would increase the risk of other psychiatric disorders.ConclusionsMajor depressive disorder might elevate the risk of dentofacial deformities, and dentofacial deformity conditions would increase the risk of the incidence of neuroticism.
| S-EPMC11319251 | biostudies-literature
Project description:IntroductionInflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are lifelong digestive diseases that severely impact patients' quality of life. The existence of a causal association between IBS and IBD remains unclear. This study aimed to determine the direction of causality between IBD and IBS by quantifying their genome-wide genetic associations and performing bidirectional two-sample Mendelian randomization (MR) analyses.MethodsGenome-wide association studies (GWAS) among a predominantly European patient cohort identified independent genetic variants associated with IBS and IBD. Two separate databases (a large GWAS meta-analysis and the FinnGen cohort) for both IBS and IBD were consulted to retrieve statistics on instrument-outcome associations. MR analyses included inverse-variance-weighted, weighted-median, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) methods, and sensitivity analyses were performed. The MR analyses were carried out for each outcome data, followed by a fixed-effect meta-analysis.ResultsGenetically predicted IBD was associated with an increased risk of IBS. Odds ratios (95% confidence intervals) for samples of 211,551 (17,302 individuals with IBD), 192,789 (7,476 Crohn's disease cases), and 201,143 (10,293 ulcerative colitis cases) individuals were 1.20 (1.00, 1.04), 1.02 (1.01, 1.03), and 1.01 (0.99, 1.03), respectively. After outlier correction using MR-PRESSO, the odds ratio for ulcerative colitis was 1.03 (1.02, 1.05) (p = 0.001). However, an association between genetically influenced IBS and IBD was not identified.DiscussionThis study confirms that IBD is causally related to IBS, which may interfere with the diagnosis and treatment of both diseases.
| S-EPMC10150057 | biostudies-literature
Project description:This study aimed to investigate the association between irritable bowel syndrome (IBS) and Parkinson's disease (PD) utilizing prospective cohort study and Mendelian randomization. The dataset contained a substantial cohort of 426,911 participants from the UK Biobank, discussing the association between IBS and PD with Cox proportional hazards models and case-control analysis while adjusting for covariates such as age, gender, ethnicity and education level. In univariate Cox regression model, the risk of PD was reduced in IBS patients (HR: 0.774, 95%CI: 0.625-0.956, P = 0.017), but the statistical significance diminished in the three models after adjusting for other variables. In a few subgroup analyses, IBS patients are less likely to develop into PD, and patients diagnosed with IBS after 2000 also had a lower risk (HR: 0.633, 95%CI: 0.403-0.994, P = 0.047) of subsequently developing PD. In addition, we matched five healthy control participants based on gender and age at the end of the study for each IBS patient diagnosed during the follow-up period, and logistic regression results (OR:1.239, 95%CI: 0.896-1.680, P = 0.181) showed that IBS was not associated with the risk of PD. Mendelian randomization did not find significant evidence of the causal relationship between IBS and Parkinson's disease (OR: 0.801, 95%CI: 0.570-1.278, P = 0.204). Overall, we suggest that IBS status is not associated with the risk of developing PD, and that these findings provide valuable insights into the clinical management and resource allocation of patients with IBS.
| S-EPMC10978991 | biostudies-literature
Project description:BackgroundObservational research has found a bidirectional relationship between major depressive disorder and gastroesophageal reflux disease; however, the causal association of this relationship is undetermined.AimsA bidirectional Mendelian randomization study was performed to explore the causal relationships between major depressive disorder and gastroesophageal reflux disease.MethodsFor the instrumental variables of major depressive disorder and gastroesophageal reflux disease, 31 and 24 single-nucleotide polymorphisms without linkage disequilibrium (r2 ≤ 0.001) were selected from relevant genome-wide association studies, respectively, at the genome-wide significance level (p ≤ 5 × 10-8). We sorted summary-level genetic data for major depressive disorder, gastroesophageal reflux disease, gastroesophageal reflux disease without esophagitis, and reflux esophagitis from meta-analysis study of genome-wide association studies involving 173,005 individuals (59,851 cases and 113,154 non-cases), 385,276 individuals (80,265 cases and 305,011 non-cases), 463,010 individuals (4360 cases and 458,650 non-cases), and 383,916 individuals (12,567 cases and 371,349 non-cases), respectively.ResultsGenetic liability to major depressive disorder was positively associated with gastroesophageal reflux disease and its subtypes. Per one-unit increase in log-transformed odds ratio of major depressive disorder, the odds ratio was 1.31 (95% confidence interval [CI], 1.19-1.43; p = 1.64 × 10-8) for gastroesophageal reflux disease, 1.51 (95% CI, 1.15-1.98; p = 0.003) for gastroesophageal reflux disease without esophagitis, and 1.21 (95% CI, 1.05-1.40; p = 0.010) for reflux esophagitis. Reverse-direction analysis suggested that genetic liability to gastroesophageal reflux disease was causally related to increasing risk of major depressive disorder. Per one-unit increase in log-transformed odds ratio of gastroesophageal reflux disease, the odds ratio of major depressive disorder was 1.28 (95% confidence interval, 1.11-1.47; p = 1.0 × 10-3).ConclusionsThis Mendelian randomization study suggests a bidirectional causal relationship between major depressive disorder and gastroesophageal reflux disease.
| S-EPMC9690029 | biostudies-literature
Project description:BackgroundRecently, observational studies have reported that gastroesophageal reflux disease (GERD) is commonly associated with irritable bowel syndrome (IBS), but the causal relationship is unclear.MethodsWe conducted a two-sample Mendelian randomization study using summary data from genome-wide association studies (GWASs) to explore a causal relationship between GERD (N cases = 129,080) and IBS (N cases = 4,605) of European ancestry. Furthermore, the inverse-variance weighted (IVW) method and a series of sensitivity analyses were used to assess the accuracy and confidence of our results.ResultsWe found a significant association of GERD with IBS (NSNP = 74; OR: 1.375; 95% CI: 1.164-1.624; p < 0.001). Reverse MR analysis showed no evidence of a causal association for IBS with GERD (NSNP = 6; OR: 0.996; 95% CI: 0.960-1.034; p = 0.845).ConclusionThis study provides evidence that the presence of GERD increases the risk of developing IBS, and it is observed from the reverse MR results that IBS did not increase the risk of GERD.
| S-EPMC11004226 | biostudies-literature