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Educational level as a cause of type 2 diabetes mellitus: Caution from triangulation of observational and genetic evidence

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Abstract

Background and objective

Education might be causal to type 2 diabetes mellitus (T2DM). We triangulated cohort and genetic evidence to consolidate the causality between education and T2DM.

Methods

We obtained observational evidence from the English Longitudinal Study of Ageing (ELSA). Self-reporting educational attainment was categorised as high (post-secondary and higher), middle (secondary), and low (below secondary or no academic qualifications) in 6,786 community-dwelling individuals aged ≥ 50 years without diabetes at ELSA wave 2, who were followed until wave 8 for the first diabetes diagnosis. Additionally, we performed two-sample Mendelian randomisation (MR) using an inverse-variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode-based estimate (WMBE) method. Steiger filtering was further applied to exclude single-nucleotide polymorphisms (SNPs) that were correlated with an outcome (T2DM) stronger than exposure (education attainment).

Results

We observed 598 new diabetes cases after 10.4 years of follow-up. The adjusted hazard ratios (95% CI) of T2DM were 1.20 (0.97–1.49) and 1.58 (1.28–1.96) in the middle- and low-education groups, respectively, compared to the high-education group. Low education was also associated with increased glycated haemoglobin levels. Psychosocial resources, occupation, and health behaviours fully explained these inverse associations. In the MR analysis of 210 SNPs (R2 = 0.0161), the odds ratio of having T2DM per standard deviation-decreasing years (4.2 years) of schooling was 1.33 (1.01–1.75; IVW), 1.23 (0.37–4.17; MR-Egger), 1.56 (1.09–2.27; WM), and 2.94 (0.98–9.09; WMBE). However, applying Steiger filtering attenuated most MR results towards the null.

Conclusions

Our inconsistent findings between cohort and genetic evidence did not support the causality between education and T2DM.

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Availability of data and material

ELSA data were made available through the UK Data Archive (https://www.ukdataservice. ac.uk/). Genetic data used in this research are publicly available from https://www.mrbase.org/.

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Acknowledgements

This research project was supported by the Thailand Science Research and Innovation Fund and the University of Phayao (Grant No. FF64-UoE039). However, the funding body did not involve the design, analysis, and interpretation of this study. The English Longitudinal Study of Ageing (ELSA) is supported by the National Institute on Ageing (grant numbers: 2RO1AG7644 and 2RO1AG017644–01A1) and a consortium of the UK government departments co-ordinated by the Office for National Statistics. Additionally, we would like to thank researchers from the MR-Base Collaboration who made the IEU GWAS database publicly available.

Funding

The original data creators, depositors or copyright holders, the funders of the Data Collections, and the UK Data Service/UK Data Archive bear no responsibility for analysing or interpreting this study.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Care, School of Pharmaceutical Sciences, University of Phayao, Phayao, 56000, Thailand

    Nat Na-Ek, Juthamanee Srithong, Authakorn Aonkhum & Suthida Boonsom

  2. Unit of Excellence On Research in Health Outcomes and Patient Safety in Elderly (U-R-HOPE), School of Pharmaceutical Sciences, University of Phayao, Phayao, 56000, Thailand

    Nat Na-Ek

  3. Unit of Excellence On Pharmacogenomic Pharmacokinetic and Pharmacotherapeutic Researches (UPPER), School of Pharmaceutical Sciences, University of Phayao, Phayao, 56000, Thailand

    Suthida Boonsom

  4. Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, Thailand

    Pimphen Charoen

  5. Integrative Computational BioScience (ICBS) Center, Mahidol University, Bangkok, 10400, Thailand

    Pimphen Charoen

  6. Department of Epidemiology and Public Health, University College London, London, WC1E 7HB, UK

    Panayotes Demakakos

Authors
  1. Nat Na-Ek
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Contributions

NN conceived the study aims and design and obtained access to ELSA data. NN, JS, and AA contributed to the literature reviewing, data cleaning, data analyses, interpretation of the findings. NN and SB developed the initial and subsequent manuscripts. PC and PD critically revised the initial manuscript, and all authors participated in further revisions. The final manuscript was read and approved by all authors before submission.

Corresponding author

Correspondence to Nat Na-Ek.

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Conflict interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Code availability

In this study, all analyses were performed using STATA version 16MR (StataCorp, LLC) package "stcox", "mixed", and "mrrobust". We also used R version 3.6 package "TwoSampleMR" for the genetic instrument extraction and harmonisation. Additional R script and STATA do-file for the analyses were available upon request.

Ethics approval

The English Longitudinal Study of Ageing has been approved by the National Research Ethics Service (London Multicentre Research Ethics Committee (MREC/01/2/91)). For the MR study, specific ethical approval has been obtained individually in the original genome-wide association studies (GWAS).

Consent to participate

Not applicable (specific consent was obtained in the original studies).

Additional information

This article belongs to the topical collection Health, Education and Psycho-Social Aspects, managed by Massimo Porta and Marina Trento.

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Na-Ek, N., Srithong, J., Aonkhum, A. et al. Educational level as a cause of type 2 diabetes mellitus: Caution from triangulation of observational and genetic evidence. Acta Diabetol 59, 127–135 (2022). https://doi.org/10.1007/s00592-021-01795-7

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  • DOI: https://doi.org/10.1007/s00592-021-01795-7

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