Using Genetics to Understand the Role of Lifestyle and Socioeconomic Factors in the Relationship Between Major Depressive Disorder and Type 2 Diabetes
- 1Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, United Kingdom
- 2Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
- 3Department of Epidemiology and Applied Clinical Research, Division of Psychiatry, University College London, London, United Kingdom
Abstract
Background: Major depressive disorder (MDD) and type 2 diabetes (T2D) are global health problems that frequently co-occur. The bidirectional causal relationship between them is well established, although the potential mediators remain understudied. Here, we investigated the role of lifestyle and socioeconomic traits as mediators of the MDD-T2D relationship using genetic data.
Methods: Using genome-wide association study (GWAS) summary statistics, we tested whether the genetic correlation (rg) between MDD (n = 2,000,702) and T2D (n = 1,812,017) was influenced by lifestyle (physical activity and sedentary time [n = 95,776], cigarettes per day [n = 618,489], and drinks per week [n = 941,280]) and socioeconomic (educational attainment [n = 293,723] and poverty factor [n = 453,689]) traits. Mendelian randomization (MR) analyses, using both GWAS and UK Biobank data, were conducted to investigate potential causal relationships. Finally, we applied mediation analysis to quantify the indirect effect of potential mediators.
Results: The strong genetic correlation between MDD and T2D (rg = 0.184, p = 3.5 × 10−37) was attenuated when accounting for cigarettes per day (partial rg = 0.098), physical activity (partial rg = 0.141), educational attainment (partial rg = 0.115), and poverty (partial rg = 0.118). MR demonstrated that a higher genetic liability to MDD and T2D was associated with higher cigarettes per day, poverty, and lower education. MR showed that higher education was associated with lower odds of MDD and T2D, while poverty was associated with higher odds of both conditions. Mediation analysis demonstrated that genetic liability to education and poverty traits substantially mediated the causal relationship in both directions: 28.67% and 24.98% for MDD→T2D and 34.3% and 29.87% for T2D→MDD, respectively.
Conclusions: Our findings highlight the role of socioeconomic traits in the MDD-T2D relationship and demonstrate both the strength and limitations of using MR for investigating complex traits. Further research incorporating gene-environment interactions, policy implications, and diverse populations is needed to better understand this relationship.
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BibTeX
@article{bala2026using,
title = {{Using Genetics to Understand the Role of Lifestyle and Socioeconomic Factors in the Relationship Between Major Depressive Disorder and Type 2 Diabetes}},
author = {Renu Bala and Anya Morris and Dale Handley and Francesco Casanova and Harry Green and Mike Elliott and Annie Jeffery and Alexandra C. Gillett and Cathryn M. Lewis and Jessica Tyrrell},
journal = {Biological psychiatry global open science},
year = {2026},
month = sep,
doi = {10.1016/j.bpsgos.2026.100822},
url = {https://europepmc.org/article/PMC/PMC13742398},
note = {CC BY},
}
RIS
TY - JOUR
TI - Using Genetics to Understand the Role of Lifestyle and Socioeconomic Factors in the Relationship Between Major Depressive Disorder and Type 2 Diabetes
AU - Renu Bala
AU - Anya Morris
AU - Dale Handley
AU - Francesco Casanova
AU - Harry Green
AU - Mike Elliott
AU - Annie Jeffery
AU - Alexandra C. Gillett
AU - Cathryn M. Lewis
AU - Jessica Tyrrell
PY - 2026
DA - 2026/09/09
JO - Biological psychiatry global open science
DO - 10.1016/j.bpsgos.2026.100822
UR - https://europepmc.org/article/PMC/PMC13742398
AB - Background: Major depressive disorder (MDD) and type 2 diabetes (T2D) are global health problems that frequently co-occur. The bidirectional causal relationship between them is well established, although the potential mediators remain understudied. Here, we investigated the role of lifestyle and socioeconomic traits as mediators of the MDD-T2D relationship using genetic data. Methods: Using genome-wide association study (GWAS) summary statistics, we tested whether the genetic correlation (rg) between MDD (n = 2,000,702) and T2D (n = 1,812,017) was influenced by lifestyle (physical activity and sedentary time [n = 95,776], cigarettes per day [n = 618,489], and drinks per week [n = 941,280]) and socioeconomic (educational attainment [n = 293,723] and poverty factor [n = 453,689]) traits. Mendelian randomization (MR) analyses, using both GWAS and UK Biobank data, were conducted to investigate potential causal relationships. Finally, we applied mediation analysis to quantify the indirect effect of potential mediators. Results: The strong genetic correlation between MDD and T2D (rg = 0.184, p = 3.5 × 10−37) was attenuated when accounting for cigarettes per day (partial rg = 0.098), physical activity (partial rg = 0.141), educational attainment (partial rg = 0.115), and poverty (partial rg = 0.118). MR demonstrated that a higher genetic liability to MDD and T2D was associated with higher cigarettes per day, poverty, and lower education. MR showed that higher education was associated with lower odds of MDD and T2D, while poverty was associated with higher odds of both conditions. Mediation analysis demonstrated that genetic liability to education and poverty traits substantially mediated the causal relationship in both directions: 28.67% and 24.98% for MDD→T2D and 34.3% and 29.87% for T2D→MDD, respectively. Conclusions: Our findings highlight the role of socioeconomic traits in the MDD-T2D relationship and demonstrate both the strength and limitations of using MR for investigating complex traits. Further research incorporating gene-environment interactions, policy implications, and diverse populations is needed to better understand this relationship.
SN - 2667-1743
ER -