Bidirectional Mendelian Randomization and Multiphenotype Genome-wide Association Studies (GWAS) Show Causality and Shared Pathophysiology Between Depression and Type 2 Diabetes
Authors' conclusion
Our results highlight the importance to prevent type 2 diabetes at the onset of depressive symptoms and the need to maintain a healthy weight in the context of its effect on depression and type 2 diabetes comorbidity.
Study context
- Population
- UK Biobank: T2D (19,344 case subjects, 463,641 control subjects), major depressive disorder (MDD) (5,262 case subjects, 86,275 control subjects) and self-reported depressive symptomsself-reported depressive symptoms 153,079
- Comparison
- Depression vs T2D: causality in both directions and shared genetics
- Outcome
- Causal effect between depression and T2D (MR)
Methodological detailstwo-step Mendelian randomization (MR) mediation analysis, expression quantitative trait locus (eQTL) analysis
- Two-step MR mediation analysis
- eQTL analysis
Main finding
As reported in the abstract
Causal effect of depression on T2D (MR)
OR, depression on T2D
1.26
95% CI 1.11–1.44P = 5.46 × 10-4
Further findings
Mediation of depression effect on T2D by BMI (two-step MR)
- Proportion mediated by BMI
- 36.5% (12.4-57.6%, P = 0.0499)
Shared genetic loci (GWAS and multiphenotype GWAS (MP-GWAS))
- MP-GWAS shared loci (TCF7L2, CDKAL1, IGF2BP2, SPRY2, CCND2-AS1, IRS1, CDKN2B-AS1)
- 7
- GWAS of T2D and depressive symptoms: no shared loci
- MDD: no significant association in GWAS or MP-GWAS
- Most MP-GWAS loci had an eQTL, incl. CCND2 in pancreatic islets and brain and IRS1 in adipose tissue
Original publication
Bidirectional Mendelian Randomization and Multiphenotype GWAS Show Causality and Shared Pathophysiology Between Depression and Type 2 Diabetes. Diabetes Care. Published 26 July 2023. doi:10.
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