Exploring the Effects of Cigarette Smoking on Inflammatory Bowel Disease Using Mendelian Randomization.
Ontology highlight
ABSTRACT: Background
Previous observational evidence has suggested an association between smoking and inflammatory bowel disease (IBD).Methods
We used observational techniques followed by Mendelian randomization to explore whether smoking is a causal factor in the development of IBD and its subtypes.Results
In those who have ever smoked, we observed increased risk of IBD and, in current smokers, we observed increased risk of Crohn disease and decreased risk of ulcerative colitis. However, our Mendelian randomization analyses found little evidence that smoking affects the development of IBD.Conclusion
Overall, our results suggest that smoking does not causally influence the risk of IBD.
SUBMITTER: Jones DP
PROVIDER: S-EPMC7809707 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Publications
Exploring the Effects of Cigarette Smoking on Inflammatory Bowel Disease Using Mendelian Randomization.
Jones Daniel P DP Richardson Tom G TG Davey Smith George G Gunnell David D Munafò Marcus R MR Wootton Robyn E RE
Crohn's & colitis 360 20200101 1
<h4>Background</h4>Previous observational evidence has suggested an association between smoking and inflammatory bowel disease (IBD).<h4>Methods</h4>We used observational techniques followed by Mendelian randomization to explore whether smoking is a causal factor in the development of IBD and its subtypes.<h4>Results</h4>In those who have ever smoked, we observed increased risk of IBD and, in current smokers, we observed increased risk of Crohn disease and decreased risk of ulcerative colitis. H ...[more]
Similar Datasets
Project description:BackgroundMalnutrition has emerged as main side effects of inflammatory bowel disease (IBD) which might also affect the prognosis of IBD. However, whether these associations are causal remains unclear. We aimed to identify the causality of IBD on malnutrition and explore the causal relationship of malnutrition and nutrients intake on IBD by using Mendelian randomization (MR).MethodsSingle nucleotide polymorphisms associated with IBD, malnutrition and nutrients intake were obtained from previous researches of genome-wide association studies (GWAS) (p < 0.00000005). MR analysis was conducted to evaluate the causality with different methods based on OR and their 95% CIs. Meanwhile, heterogeneity, pleiotropy and MR-PRESSO were used for instrumental variables evaluation.ResultsThe results of MR analysis revealed that IBD, both Crohn disease (CD) and ulcerative colitis (UC), could directly impact the incidence of malnutrition (p-value <0.01). CD is directly related to nutrients such as sugar, fat, VA, VC, VD and zinc, while UC is correlated with carbohydrate, fat, VB12, VC, VD, VE, iron, zinc and magnesium. However, our results suggested that malnutrition could not affect the risk of IBD directly (p > 0.05). Further analysis showed similar results that nutrients intake had no direct effect on IBD, neither CD or UC.ConclusionOur results indicated that IBD increases the risk of malnutrition, however, malnutrition and nutrients intake might not directly affect the progression of IBD.
| S-EPMC11349745 | biostudies-literature
Project description:Traditional observational studies have indicated a link between specific food intakes and inflammatory bowel disease (IBD), but the nature of such links remains unknown. We sought to assess the potential causal relationship between food intakes and IBD risk using Mendelian randomization methods. This study used summary statistics data from large-scale genome-wide association studies (GWAS) on food intakes, Crohn's disease (CD), and ulcerative colitis (UC). In the primary analysis, we used the inverse variance-weighted method to determine whether specific food was causal for CD and UC. In addition, we also ran four other Mendelian randomization methods, including MR Egger, weighted median, maximum likelihood, and weighted mode as a complement. The primary analysis showed that high consumption of poultry (OR, 3.696; 95% CI, 1.056-12.937; p = 0.041) and cereal (OR, 2.449; 95% CI, 1.094-5.482; p = 0.029) had a significant causal association with CD, while high oily fish intake level was found to be statistically significantly associated with the risk of UC (OR, 1.482; 95% CI, 1.002-2.194; p = 0.049). This MR study provides evidence of a potential causal link between certain food intake and CD and UC.
| S-EPMC9536736 | biostudies-literature
Project description:Objective: Although previous epidemiological studies have reported substantial links between inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and celiac disease (CeD), the causal relationship between the two remains unknown. The purpose of the current study was to evaluate the bidirectional causation between IBD and CeD using Mendelian randomization (MR). Method: We obtained genome-wide association study (GWAS) summary data of IBD (CD and UC) and CeD of thoroughly European ancestry from the IEU GWAS database. We screened eligible instrumental variables (IVs) according to the three assumptions of MR. MR was performed using MR-Egger, weighted median (WM), and inverse variance weighted (IVW) methods. The MR-Egger intercept and MR-PRESSO method investigated the horizontal pleiotropy effect. A leave-one-out analysis was performed to prevent bias caused by a single SNP. Results: The study assessed a bidirectional causal effect between CD and CeD; CD increased the risk of CeD (IVW odds ratio (OR) = 1.27, 95% confidence interval (CI) = 1.19-1.35, p = 3.75E-13) and vice-a-versa (IVW OR = 1.09, 95% CI = 1.05-1.13, p = 1.39E-05). Additionally, CeD was influenced by IBD (IVW OR = 1.24, 95% CI = 1.16-1.34, p = 9.42E-10) and UC (IVW OR = 0.90, 95% CI = 0.83-0.98, p = 0.017). However, we observed no evidence of a causal relationship between CeD and IBD (IVW OR = 1.00, 95% CI = 0.97-1.04, p = 0.900) or UC (IVW OR = 0.96, 95% CI = 0.92-1.02, p = 0.172). Conclusion: The present study revealed that IBD and CeD have a bidirectional causal relationship. However, it is slightly different from the results of previous observational studies, recommending that future studies focus on the mechanisms of interaction between CD and CeD.
| S-EPMC9437575 | biostudies-literature
Project description:ObjectivesPrevious studies have confirmed a link between specific inflammatory cytokines and inflammatory bowel disease (IBD), but the causal relationship between them is not completely clear. This Mendelian Randomization (MR) study aims to evaluate the causal relationship between 18 inflammatory cytokines and inflammatory bowel disease.MethodTwo-sample Mendelian randomization utilized genetic variances associated with IBD from two extensive publicly available genome-wide association studies (GWAS) (Crohn's Disease (CD): 12,194 cases and 28,072 controls; Ulcerative Colitis (UC): 12,336 cases and 33,609 controls). The data of inflammatory cytokines was acquired from a GWAS including 8,293 healthy participants. We used inverse variance weighted method, MR-Egger, weighted median, simple model and weighted model to evaluate the causal relationship between inflammatory cytokines and IBD. Sensitivity analysis includes heterogeneity and pleiotropy analysis to evaluate the robustness of the results.ResultsThe findings indicated suggestive positive associations between Interleukin-13 (IL-13) and macrophage migration inhibitory factor (MIF) with CD (odds ratio, OR: 1.101, 95%CI: 1.021-1.188, p = 0.013; OR: 1.134, 95%CI: 1.024-1.255, p = 0.015). IL-13 also displayed a significant positive correlation with UC (OR: 1.099, 95%CI: 1.018-1.186, p = 0.016). Stem cell factor (SCF) was suggested to be associated with the development of both CD and UC (OR: 1.032, 95%CI: 0.973-1.058, p = 0.012; OR: 1.038, 95%CI: 1.005-1.072, p = 0.024).ConclusionThis study proposes that IL-13 may be a factor correlated with the etiology of IBD (CD and UC), while MIF just be specifically associated with CD. Additionally, SCF appears more likely to be involved in the downstream development of IBD (CD and UC).
| S-EPMC10822978 | biostudies-literature
Project description:Inflammatory Bowel Disease (IBD) is a severe relapsing inflammation of the gastrointestinal tract. The association between fatty acids (FAs) and IBD is controversial and it remains unclear whether there is a causal relationship between them. Mendelian randomization (MR) analysis was province/state for affiliations from the same country performed to clarify the causality. Eligible single nucleotide polymorphisms were selected as instrumental variables from six Genome-wide association studies, involving 114,999 individuals in UK Biobank. The summary-level data on IBD, including Crohn's disease (CD) and ulcerative colitis (UC), were obtained from the International Inflammatory Bowel Disease Genetics Consortium with 20,883 and 27,432 individuals involved. The primary inverse variance weighted (IVW) method as well as other supplementary analysis ones were adopted to evaluate the causal relationship between diverse FAs and IBD. The tests for heterogeneity and pleiotropy, and Leave-one-out analysis were adopted to verify the stability of the results. Omega-3 FA was found to have a causal effect on UC instead of CD. For each Standard Deviation increase in Omega-3 FA genetic levels, the risk of ulcerative colitis was found to be reduced by 39.9% by the IVW method (p = 1.766 × 10-4), by 57.8% by the MR Egger (p = 1.11 × 10-2), by 51.5% by the Weighted median estimator (p = 7.706 × 10-4), by 39% by the Maximum likelihood estimation (p = 3.262 × 10-4), and by 54.5% by the penalized weighted median estimator (p = 1.628 × 10-4). No causal relationship was found between other FAs (including total FA, saturated FA, polyunsaturated FA, monounsaturated FA and omega-6 FA) and IBD. The pleiotropic test and Leave-one-out analysis both proved the validity and reliability of these MR analyses. Omega-3 FA was observed to have a protective effect against UC, providing a new perspective on the investigation of the associations between FAs and IBD.
| S-EPMC9320846 | biostudies-literature
Project description:BackgroundAlthough epidemiological studies have shown a positive relationship between inflammatory bowel disease (IBD) and risk of cardiovascular disease (CVD) outcomes, a solid causal relationship has not been established. Thus, a two-sample Mendelian randomization (MR) study was conducted to explore the potential causal effect between IBD and CVD outcomes.MethodsWe performed a two-sample MR analysis to analyze the causal effect of the IBD on CVD outcome by using summary-level genome-wide association studies of European descent. The inverse-variance weighted (IVW) method was used as the main MR analysis, with complementary analyses of MR Egger, maximum likelihood, weighted median, penalized weighted media, simple mode, weighted mode, and MR-PRESSO methods. Multiple sensitivity analyses were used to evaluate the robustness of our results.ResultsAll P-values were greater than 0.05 in the IVW method, showing no evidence of a causal association between circulating IBD and CVD. Similar results were observed by using other MR methods. No evidence of heterogeneity, pleiotropy, or outlier single-nucleotide polymorphisms was detected. Sensitivity analyses demonstrated the robustness of the results.ConclusionThe findings of this study provided no evidence to support that IBD has a large effect on risk of CVD outcomes, which is in contrast to many previous observational reports. Further studies are needed to determine the potential mechanism of association identified in observational studies.
| S-EPMC9478388 | biostudies-literature
Project description:BackgroundIridocyclitis (IC) is a common extraintestinal manifestation of inflammatory bowel disease (IBD). Observational studies showed patients with ulcerative colitis (UC) and Crohn's disease (CD) both have a higher risk of IC. However, due to the inherent limitations of observational studies, the association and its directionality between the two forms of IBD and IC remain undiscerned.MethodsGenetic variants for IBD and IC were selected as instruments from genome-wide association studies (GWAS) and FinnGen database as instrumental variables, respectively. A bidirectional Mendelian randomization (MR) and multivariable MR were performed successively. Three different MR methods were performed to determine the causal association, including inverse-variance weighted (IVW), MR Egger, and weighted median, whereas IVW was used as the main analysis. Different methods for sensitivity analysis were used, including MR-Egger intercept test, MR Pleiotropy RESidual Sum and Outlier test, Cochran's Q test, and leave-one-out analysis.ResultsBidirectional MR suggested both UC and CD were positively associated with IC as a whole, acute and subacute IC, and chronic IC. However, in the MVMR analysis, only the association from CD to IC remained stable. In the reverse analysis, no association was observed from IC to UC or CD.ConclusionsBoth UC and CD are associated with an increased risk of IC compared with healthy individuals. However, the association between CD and IC is stronger. In the reverse direction, patients with IC do not suffer a higher risk of UC or CD. We emphasize the importance of ophthalmic examinations for IBD patients, especially for CD patients.
| S-EPMC9960523 | biostudies-literature
Project description:The association between rosacea and inflammatory bowel disease (IBD) has been studied in previous observational studies. It is unclear, however, whether the association is causal or not. Independent genetic variants for IBD were chosen as instruments from published Genome-wide association studies (GWAS) studies involving 38,155 cases with an IBD diagnosis and 48,485 controls in order to investigate the causal effect of IBD on rosacea. Summarized data for rosacea were gathered from various GWAS studies that included 1195 cases and 211,139 controls without rosacea. Reverse-direction Mendelian randomization (MR) analysis was done to investigate the relationship between genetically proxied rosacea and IBD. With the use of the inverse variance-weighted (IVW), MR-Egger, and weighted median approaches, a 2-sample Mendelian randomization study was carried out. Analysis of heterogeneity and sensitivity was performed to examine the pleiotropy and robustness of effect estimates. The forward-direction of the MR study was to reveal that genetic predisposition to IBD including its two main subtypes: Crohn's disease (CD) and ulcerative colitis (UC) was associated with an increased risk of rosacea. The reverse-direction MR analyses did not demonstrate that a genetic predisposition to rosacea was associated with total IBD, UC and CD. Our findings provided evidence for a causal impact of IBD, UC, and CD on rosacea, but not vice versa. The elevated incidence of rosacea in patients with IBD should be recognized by doctors to make an early diagnosis and initiate specialized therapy.
| S-EPMC10492847 | biostudies-literature
Project description:BackgroundAccumulating evidence has shown that patients with inflammatory bowel disease (IBD) have liver function abnormalities and are susceptible to liver diseases. However, the existence of a causal relationship between IBD and liver function or disease remains unclear.MethodsA two-sample Mendelian randomization (MR) analysis was performed using genetic associations from publicly available genome-wide association studies (GWAS). These associations encompass ulcerative colitis (UC), Crohn's disease (CD), liver function traits, and liver disease phenotypes. The liver function traits comprised hepatic biochemistries, percent liver fat, and liver iron content from the UK Biobank. Furthermore, the liver disease phenotypes included cholelithiasis, non-alcoholic fatty liver disease (NAFLD), primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC) in cohorts of European ancestry. The primary estimation used the inverse-variance weighted method, with GWAS of C-reactive protein (CRP) in the UK Biobank serving as a positive control outcome.ResultsGenetically predicted UC is causally associated with decreased levels of albumin (ALB) and liver iron content, while genetically predicted CD is causally associated with increased levels of alkaline phosphatase (ALP). Moreover, genetically predicted UC or CD increases the risk of PSC, and CD increases the risk of PBC. Neither UC nor CD causally increases the risk of cholelithiasis and NAFLD.ConclusionUC affects the levels of ALB and liver iron content, while CD affects the levels of ALP. Both UC and CD increase the risk of PSC, and CD increases the risk of PBC.
| S-EPMC10827874 | biostudies-literature
Project description:BackgroundDespite growing evidence indicating that patients with inflammatory bowel disease (IBD) have an increased risk of atrial fibrillation (AF), owing to the potential biases of confounding effects and reverse causation, the specific relationship between IBD and AF remains controversial. The aim of this study is to determine whether there is a causal effect of IBD on AF.MethodsA two-sample Mendelian randomization (MR) study was performed to evaluate the causal effect of IBD on AF. Statistical summaries for the associations between single nucleotide polymorphisms (SNPs) and traits of interest were obtained from independent consortia with European populations. The dataset of IBD was acquired from genome-wide association studies (GWAS), including more than 75,000 cases and controls. A GWAS with 60,620 AF cases and 970,216 controls was used to identify genetic variation underlying AF. The causal effect was estimated using the multiplicative random effects inverse-variance weighted method (IVW), followed by sensitivity analysis.ResultsUsing 81 SNPs, there was no evidence to suggest an association between genetically predicted IBD and risk of AF with multiplicative random-effects IVW MR analysis (odds ratio = 1.0000, 95% confidence interval: 0.9994 1.0005, p = 0.88).ConclusionAs opposed to current assumptions, no substantial evidence was found to support a causal role of IBD in the development of AF.
| S-EPMC8109086 | biostudies-literature