Dataset Information

Causal Associations Between Tobacco, Alcohol Use and Risk of Infectious Diseases: A Mendelian Randomization Study.

ABSTRACT:

Introduction

The causal effects of smoking and alcohol use on the risk of infectious diseases are unclear, and it is hard investigate them in an observational study due to the potential confounding factors. The aim of this study was to use Mendelian randomization (MR) techniques to assess the causalities between smoking, alcohol use and risk of infectious diseases.

Methods

Univariable and multivariable MR analyses were performed using genome-wide association data for the age of initiation of regular smoking (AgeSmk, N = 341,427), smoking initiation (SmkInit, N = 1,232,091), cigarettes per day (CigDay, N = 337,334), lifetime smoking (LifSmk, N = 462,690), drinks per week (DrnkWk, N = 941,280), sepsis (N = 486,484), pneumonia (N = 486,484), upper respiratory tract infection (URTI, N = 486,484) and urinary tract infection (UTI, N = 486,214) among individuals of European ancestry. Independent genetic variants that were significantly (P < 5 × 10^-8) associated with each exposure were considered as instruments. The inverse-variance-weighted method was used in the primary analysis, which was followed by a series of sensitivity analyses.

Results

Genetically predicted SmkInit was associated with an increased risk of sepsis (OR 1.353, 95% CI 1.079-1.696, P = 0.009), pneumonia (OR 1.770, 95% CI 1.464-2.141, P = 3.8 × 10^-9) and UTI (OR 1.445, 95% CI 1.184-1.764, P = 3 × 10^-4). Moreover, genetically predicted CigDay was associated with a higher risk of sepsis (OR 1.403, 95% CI 1.037-1.898, P = 0.028) and pneumonia (OR 1.501, 95% CI 1.167-1.930, P = 0.00156). Furthermore, genetically predicted LifSmk was associated with an increased risk of sepsis (OR 2.200, 95% CI 1.583-3.057, P = 2.63 × 10^-6), pneumonia (OR 3.462, 95% CI 2.798-4.285, P = 3.28 × 10^-30), URTI (OR 2.523, 95% CI 1.315-4.841, P = 0.005) and UTI (OR 2.036, 95% CI 1.585-2.616, P = 3.0 × 10^-8). However, there was no significant causal evidence for genetically predicted DrnkWk in sepsis, pneumonia, URTI or UTI. Multivariable MR analyses and sensitivity analyses showed that the above results for causal association estimations were robust.

Conclusion

In this MR study, we demonstrated the causal association between tobacco smoking and risk of infectious diseases. However, no evidence was found to support causality between alcohol use and the risk of infectious diseases.

SUBMITTER: Zhu H

PROVIDER: S-EPMC10017901 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

Causal Associations Between Tobacco, Alcohol Use and Risk of Infectious Diseases: A Mendelian Randomization Study.

Zhu Hongxiang H Zhan Xiaohui X Wang Congjie C Deng Yuying Y Li Xiaoping X Song Linru L Zhao Lingyan L

Infectious diseases and therapy 20230302 3

<h4>Introduction</h4>The causal effects of smoking and alcohol use on the risk of infectious diseases are unclear, and it is hard investigate them in an observational study due to the potential confounding factors. The aim of this study was to use Mendelian randomization (MR) techniques to assess the causalities between smoking, alcohol use and risk of infectious diseases.<h4>Methods</h4>Univariable and multivariable MR analyses were performed using genome-wide association data for the age of in ...[more]

PMID: 36862322

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Project description:Several observational studies have revealed an association between autoimmune diseases (AIDs) and colorectal cancer (CRC), although their causal association remained controversial. Therefore, our study used a two-sample Mendelian randomization (MR) analysis to verify the causal association between AIDs and CRC. We employed three common MR approaches, including inverse variance weighted (IVW), weighted median, and MR-Egger methods, to assess the causal association between type 1 diabetes (T1D), systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, juvenile idiopathic arthritis, celiac disease, and primary sclerosing cholangitis (PSC) and CRC. The reverse MR analysis was performed to assess the possibility of reverse causation. To evaluate the validity of the analysis, we also performed sensitivity analysis, such as the heterogeneity test, the horizontal pleiotropy test, and the leave-one-out sensitivity analysis, and validated the results in the validation cohort. Our results showed that genetically predicted T1D was nominally associated with a lower risk of CRC (IVW OR = 0.965, 95% CI = 0.939-0.992, P = 0.012). However, genetic susceptibility to psoriasis nominally increased the risk of CRC (IVW OR = 1.026, 95% CI = 1.002-1.050, P = 0.037). Genetically predicted PSC had a significant causal effect on the increasing risk of CRC (IVW OR = 1.038, 95% CI = 1.016-1.060, P = 5.85 × 10-4). Furthermore, the MR analysis between PSC and the CRC validation cohort indicated consistent results. We found no causal association between genetically predicted other five AIDs and CRC (P > 0.05). The results of reverse MR analysis showed that genetically predicted CRC had no causal effect on T1D, psoriasis, and PSC (P > 0.05). The sensitivity analysis demonstrated that the results of the MR analysis were reliable. Our findings help to understand the causal association between AIDs and CRC, which deserves further investigation.

Project description:BackgroundThe presence of type 1 diabetes mellitus (T1DM) has been demonstrated to pose an increased risk for developing cardiovascular diseases (CVDs). However, the causal relationships between T1DM and CVDs remain unclear due to the uncontrolled confounding factors and reverse causation bias of the observational studies.MethodsSummary statistics of T1DM and seven CVDs from the largest available genome-wide association studies (GWAS) of European ancestry and FinnGen biobank were extracted for the primary MR analysis, and the analysis was replicated using UK biobank (UKBB) for validation. Three complementary methods: inverse variance weighted (IVW), weighted median, and MR-Egger were used for the MR estimates. The potential pleiotropic effects were assessed by MR-Egger intercept and MR-PRESSO global test. Additionally, multivariable MR (MVMR) analysis was performed to examine whether T1DM has independent effects on CVDs with adjustment of potential confounding factors. Moreover, a two-step MR approach was used to assess the potential mediating effects of these factors on the causal effects between T1DM and CVDs.ResultsCausal effects of T1DM on peripheral atherosclerosis (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.02-1.10; p = 0.002)] and coronary atherosclerosis (OR = 1.03, 95% CI: 1.01-1.05; p = 0.001) were found. The results were less likely to be biased by the horizontal pleiotropic effects (both p values of MR-Egger intercept and MR-PRESSO Global test > 0.05). In the following MVMR analysis, we found the causal effects of T1DM on peripheral atherosclerosis and coronary atherosclerosis remain significant after adjusting for a series of potential confounding factors. Moreover, we found that hypertension partly mediated the causal effects of T1DM on peripheral atherosclerosis (proportion of mediation effect in total effect: 11.47%, 95% CI: 3.23-19.71%) and coronary atherosclerosis (16.84%, 95% CI: 5.35-28.33%). We didn't find significant causal relationships between T1DM and other CVDs, including heart failure (HF), coronary artery disease (CAD), atrial fibrillation (AF), myocardial infarction (MI) and stroke. For the reverse MR from CVD to T1DM, no significant causal relationships were identified.ConclusionThis MR study provided evidence supporting the causal effect of T1DM on peripheral atherosclerosis and coronary atherosclerosis, with hypertension partly mediating this effect.

Dataset Information

Causal Associations Between Tobacco, Alcohol Use and Risk of Infectious Diseases: A Mendelian Randomization Study.

Introduction

Methods

Results

Conclusion

Publications

Causal Associations Between Tobacco, Alcohol Use and Risk of Infectious Diseases: A Mendelian Randomization Study.

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