Investigating whether smoking and alcohol behaviours influence risk of type 2 diabetes using a Mendelian randomisation study

Zoe E. Reed, Hannah M. Sallis, Rebecca C. Richmond, Angela S. Attwood, Deborah A. Lawlor, Marcus R. Munafò

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1 Citation (SciVal)

Abstract

Previous studies suggest that smoking and higher alcohol consumption are associated with greater type 2 diabetes (T2D) risk. However, studies examining whether this reflects causal relationships are limited and often do not consider continuous glycaemic traits. We conducted both two-sample and one-sample Mendelian randomisation (MR), using publicly available GWAS data and UK Biobank data, respectively, to examine the potential causal effects of lifetime smoking index (LSI) and alcoholic drinks per week (DPW) on T2D and continuous traits (fasting glucose, fasting insulin and glycated haemoglobin, HbA1c). Two-sample MR results suggested possible causal effects of higher LSI on T2D risk (OR per 1SD higher LSI: 1.42, 95% CI 1.22 to 1.64); however, sensitivity analyses did not consistently support this finding. There was no robust evidence that higher DPW influenced T2D risk (OR per 1 SD higher log-transformed DPW: 1.04, 95% CI 0.40 to 2.65). There was evidence of a potential causal effect on higher fasting glucose (difference in mean fasting glucose in mmol/l per 1SD higher log-transformed DPW: 0.34, 95% CI 0.09 to 0.59), though, this was attenuated when accounting for body mass index (BMI), suggesting BMI confounding might explain the potential effect. One-sample MR results suggested a possible causal effect of higher DPW on T2D risk (OR per 1 SD higher log-transformed DPW: 1.71, 95% CI 1.24 to 2.36), but lower HbA1c levels (difference in mean SD of log transformed HbA1c (mmol/mol) per 1 SD higher log-transformed DPW: −0.07, 95% CI −0.11 to −0.02). Our results suggest effective public health interventions to prevent and/or reduce smoking and alcohol consumption are unlikely to reduce T2D prevalence.

Original languageEnglish
Article number7985
JournalScientific Reports
Volume15
Issue number1
Early online date7 Mar 2025
DOIs
Publication statusE-pub ahead of print - 7 Mar 2025

Data Availability Statement

Access details for the GWAS data used in this study are outlined in Supplementary Table S5. UK Biobank data are available through a procedure described at http://www.ukbiobank.ac.uk/using-the-resource/. Analysis code is available from the University of Bristol’s Research Data Repository (http://data.bris.ac.uk/data/), at: https://doi.org/10.5523/bris.3jxmv9snqzflp26nt29graal54.

Acknowledgements

This research has been conducted using data from UKBB (project ID: 9142), a major biomedical database (http://www.ukbiobank.ac.uk/). We would like to thank the research participants and employees of 23andMe, inc. for making this work possible. For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission. The type 2 diabetes GWAS included data from the Million Veteran Program (MVP), Office of Research and Development, Veterans Health Administration, and was supported by the Veterans Administration (VA). The authors thank MVP staff, researchers, and volunteers, who have contributed to MVP, and especially participants who previously served their country in the military and now generously agreed to enroll in the study. (See https://www.research.va.gov/mvp/ for more details). The MVP GWAS data was provided through dbGaP under Accession Number phs001672.

Funding

This work was supported in part by the UK Medical Research Council Integrative Epidemiology Unit at the University of Bristol (Grant ref: MC_UU_00032/5 and MC_UU_00032/7). HMS was supported by the European Research Council (Grant ref: 758813 MHINT). RCR was supported by Cancer Research UK (grant number C18281/A29019). DAL’s contribution is supported by the British Heart Foundation (CH/F/20/90003 and AA/18/1/34219). MRM was supported by the National Institute for Health Research Bristol Biomedical Research Centre. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care.

FundersFunder number
Medical Research CouncilMC_UU_00032/5 , MC_UU_00032/7

Keywords

  • Alcohol
  • Glycaemic traits
  • Mendelian randomisation
  • Smoking
  • Type 2 diabetes
  • UK Biobank

ASJC Scopus subject areas

  • General

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