Dataset Information

Unravelling the complex causal effects of substance use behaviours on common diseases.

ABSTRACT:

Background

Substance use behaviours (SUB) including smoking, alcohol consumption, and coffee intake are associated with many health outcomes. However, whether the health effects of SUB are causal remains controversial, especially for alcohol consumption and coffee intake.

Methods

In this study, we assess 11 commonly used Mendelian Randomization (MR) methods by simulation and apply them to investigate the causal relationship between 7 SUB traits and health outcomes. We also combine stratified regression, genetic correlation, and MR analyses to investigate the dosage-dependent effects.

Results

We show that smoking initiation has widespread risk effects on common diseases such as asthma, type 2 diabetes, and peripheral vascular disease. Alcohol consumption shows risk effects specifically on cardiovascular diseases, dyslipidemia, and hypertensive diseases. We find evidence of dosage-dependent effects of coffee and tea intake on common diseases (e.g., cardiovascular disease and osteoarthritis). We observe that the minor allele effect of rs4410790 (the top signal for tea intake level) is negative on heavy tea intake (b̂GWAS=-0.091,s.e.=0.007,P=4.90×10-35) but positive on moderate tea intake (b̂GWAS=0.034,s.e.=0.006,P=3.40×10-8) , compared to the non-tea-drinkers.

Conclusion

Our study reveals the complexity of the health effects of SUB and informs design for future studies aiming to dissect the causal relationships between behavioural traits and complex diseases.

SUBMITTER: Xue A

PROVIDER: S-EPMC10933313 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Unravelling the complex causal effects of substance use behaviours on common diseases.

Xue Angli A Zhu Zhihong Z Wang Huanwei H Jiang Longda L Visscher Peter M PM Zeng Jian J Yang Jian J

Communications medicine 20240312 1

<h4>Background</h4>Substance use behaviours (SUB) including smoking, alcohol consumption, and coffee intake are associated with many health outcomes. However, whether the health effects of SUB are causal remains controversial, especially for alcohol consumption and coffee intake.<h4>Methods</h4>In this study, we assess 11 commonly used Mendelian Randomization (MR) methods by simulation and apply them to investigate the causal relationship between 7 SUB traits and health outcomes. We also combine ...[more]

PMID: 38472333

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Project description:Observationally, higher caffeine consumption is associated with poorer sleep and insomnia. We investigated whether these associations are a result of shared genetic risk factors and/or (possibly bidirectional) causal effects. Summary-level data were available from genome-wide association studies on caffeine intake (n = 91 462), plasma caffeine and caffeine metabolic rate (n = 9876), sleep duration and chronotype (being a "morning" versus an "evening" person) (n = 128 266), and insomnia complaints (n = 113 006). First, genetic correlations were calculated, reflecting the extent to which genetic variants influencing caffeine consumption and those influencing sleep overlap. Next, causal effects were estimated with bidirectional, two-sample Mendelian randomization. This approach utilizes the genetic variants most robustly associated with an exposure variable as an "instrument" to test causal effects. Estimates from individual variants were combined using inverse-variance weighted meta-analysis, weighted median regression and MR-Egger regression. We found no clear evidence for a genetic correlation between caffeine intake and sleep duration (rg = 0.000, p = .998), chronotype (rg = 0.086, p = .192) or insomnia complaints (rg = -0.034, p = .700). For plasma caffeine and caffeine metabolic rate, genetic correlations could not be calculated because of the small sample size. Mendelian randomization did not support causal effects of caffeine intake on sleep, or vice versa. There was weak evidence that higher plasma caffeine levels causally decrease the odds of being a morning person. Although caffeine may acutely affect sleep when taken shortly before bedtime, our findings suggest that a sustained pattern of high caffeine consumption is more likely to be associated with poorer sleep through shared environmental factors. Future research should identify such environments, which could aid the development of interventions to improve sleep.

Project description:Cannabis use disorder (CanUD) has increased with the legalization of the use of cannabis. Around 20% of individuals using cannabis develop CanUD, and the number of users has grown with increasing ease of access. CanUD and other substance use disorders (SUDs) are associated phenotypically and genetically. We leveraged new CanUD genomics data to undertake genetically-informed analyses with unprecedented power, to investigate the genetic architecture and causal relationships between CanUD and lifetime cannabis use with risk for developing SUDs and substance use traits. Analyses included calculating local and global genetic correlations, genomic structural equation modeling (genomicSEM), and Mendelian Randomization (MR). Results from the genetic correlation and genomicSEM analyses demonstrated that CanUD and cannabis use differ in their relationships with SUDs and substance use traits. We found significant causal effects of CanUD influencing all the analyzed traits: opioid use disorder (OUD) (Inverse variant weighted, IVW β = 0.925 ± 0.082), problematic alcohol use (PAU) (IVW β = 0.443 ± 0.030), drinks per week (DPW) (IVW β = 0.182 ± 0.025), Fagerström Test for Nicotine Dependence (FTND) (IVW β = 0.183 ± 0.052), cigarettes per day (IVW β = 0.150 ± 0.045), current versus former smokers (IVW β = 0.178 ± 0.052), and smoking initiation (IVW β = 0.405 ± 0.042). We also found evidence of bidirectionality showing that OUD, PAU, smoking initiation, smoking cessation, and DPW all increase risk of developing CanUD. For cannabis use, bidirectional relationships were inferred with PAU, smoking initiation, and DPW; cannabis use was also associated with a higher risk of developing OUD (IVW β = 0.785 ± 0.266). GenomicSEM confirmed that CanUD and cannabis use load onto different genetic factors. We conclude that CanUD and cannabis use can increase the risk of developing other SUDs. This has substantial public health implications; the move towards legalization of cannabis use may be expected to increase other kinds of problematic substance use. These harmful outcomes are in addition to the medical harms associated directly with CanUD.

Dataset Information

Unravelling the complex causal effects of substance use behaviours on common diseases.

Background

Methods

Results

Conclusion

Publications

Unravelling the complex causal effects of substance use behaviours on common diseases.

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