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

Angli Xue; Zhihong Zhu; Huanwei Wang; Longda Jiang; Peter M Visscher; Jian Zeng; Jian Yang

doi:10.1038/s43856-024-00473-3

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

Commun Med (Lond). 2024 Mar 12;4(1):43. doi: 10.1038/s43856-024-00473-3.

Authors

Angli Xue^{1

2

3}, Zhihong Zhu^{1

4}, Huanwei Wang¹, Longda Jiang¹, Peter M Visscher¹, Jian Zeng¹, Jian Yang^{5

6

7}

Affiliations

¹ Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
² Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
³ School of Biomedical Sciences, University of New South Wales, Sydney, NSW, 2052, Australia.
⁴ National Centre for Register-Based Research, Aarhus University, Aarhus V, 8210, Denmark.
⁵ Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia. jian.yang@westlake.edu.cn.
⁶ School of Life Sciences, Westlake University, Hangzhou, Zhejiang, 310024, China. jian.yang@westlake.edu.cn.
⁷ Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, 310024, China. jian.yang@westlake.edu.cn.

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 $({\hat{b}}_{G W A S} = - 0.091, s . e . = 0.007, P = 4.90 \times 10^{- 35})$ but positive on moderate tea intake $({\hat{b}}_{G W A S} = 0.034, s . e . = 0.006, P = 3.40 \times 10^{- 8})$ , 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.

Plain language summary

Many people smoke or consume alcohol, coffee and tea. The relationship between using these types of substance and the development of different diseases is not well understood. Previous studies have suggested that differences in genetics, i.e. inherited characteristics, could have an impact on how each substance impacts a particular person’s health. We used a method called Mendelian Randomization to look at the impact of consuming tobacco, alcohol, coffee and tea on the development of various common diseases using genetic information. We found that relationships were complicated and many were dosage-dependent, but that consumption of a large amount of all substances tended to have negative health impacts regardless of lifestyle, behavioural or inherited characteristics.

Abstract

Plain language summary

Grants and funding