ArticleDiabetes care2023
Bidirectional Mendelian Randomization and Multiphenotype GWAS Show Causality and Shared Pathophysiology Between Depression and Type 2 Diabetes.
Article in Diabetes care, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- Identification ofDepression and anxiety · 2025Pooled it
- Association of long-term depressive burden with incident cardiometabolic multimorbidity: a prospective study in middle-aged and older adults across three continents.Journal of global health · 2026Article
- Association between antidepressant use and the risk of type 2 diabetes: a multi-stage Mendelian randomization study.European archives of psychiatry and clinical neuroscience · 2026Article
- Association Between Metabolic Parameters and FTO Alpha-Ketoglutarate-Dependent Dioxygenase (International journal of molecular sciences · 2026Article
- Genetic and sociodemographic factors associated with trajectories of physical and mental health multimorbidity in a South Asian cohort in the UK: A multistate modelling analysis.PLoS medicine · 2026Article
- Genetic heterogeneity affects the risk of incident depression, comorbidity, and response to environment: A prospective trajectory study.Psychological medicine · 2026Article
- Association of triglyceride-glucose index with anxiety in first-episode, drug-naïve major depressive disorder: role of subclinical hypothyroidism.European archives of psychiatry and clinical neuroscience · 2026Article
- Article
- eQTL analysis: A bridge from genome to mechanism.Genes & diseases · 2026Review
- Testing bidirectional associations of major depressive disorder with medical conditions: two-sample Mendelian randomization study.Npj mental health research · 2026Article
- Integrative analysis of single-cell and bulk RNA sequencing data using machine learning identifies PTGDS as a key subsynovial fibroblast gene in osteoarthritis.Journal of molecular histology · 2026Article
- Leveraging transdiagnostic genetic liability to psychiatric disorders to dissect clinical outcomes of anorexia nervosa.Molecular psychiatry · 2026Article
- Exploration and Validation of the Diagnostic Potential of the Circadian Rhythm-Related Genes CCL23 and VNN1 in Adolescents with Depressive Disorder.Molecular neurobiology · 2026Article
- Depressive symptoms and cardiometabolic diseases in Chinese middle-aged and older adults: a longitudinal cross-lagged analysis.BMC public health · 2026Article
- Sodium-Glucose Cotransporter-2 Inhibitors in Mood Disorders: A Narrative Review of Mechanisms, Evidence, and Challenges.Neuropsychiatric disease and treatment · 2026Review
- Genetic associations and candidate functional genes linking depression and obesity: a multi-omics integrative study.Frontiers in genetics · 2026Article
- Development and Validation of a Risk Screening Model for Depressive Symptoms in Older Inpatients: A Cross-Sectional Study.Clinical interventions in aging · 2026Article
- Comorbidity Between Mood Disorders and Chronic Somatic Diseases, With a Focus on Cardiometabolic Disease, and Its Mechanistic Crosstalk.Depression and anxiety · 2026Review
- Prospective associations between diabetes and depressive symptoms across European regions: a secondary analysis of ELSA, TILDA, and SHARE datasets.European journal of public health · 2025Article
- Causal relationships between blood metabolites and glioblastoma risk: a large-scale Mendelian randomization study.Discover oncology · 2025Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveDepression is a common comorbidity of type 2 diabetes. We assessed the causal relationships and shared genetics between them. RESEARCH DESIGN AND
methodsWe applied two-sample, bidirectional Mendelian randomization (MR) to assess causality between type 2 diabetes and depression. We investigated potential mediation using two-step MR. To identify shared genetics, we performed 1) genome-wide association studies (GWAS) separately and 2) multiphenotype GWAS (MP-GWAS) of type 2 diabetes (19,344 case subjects, 463,641 control subjects) and depression using major depressive disorder (MDD) (5,262 case subjects, 86,275 control subjects) and self-reported depressive symptoms (n = 153,079) in the UK Biobank. We analyzed expression quantitative trait locus (eQTL) data from public databases to identify target genes in relevant tissues.
resultsMR demonstrated a significant causal effect of depression on type 2 diabetes (odds ratio 1.26 [95% CI 1.11-1.44], P = 5.46 × 10-4) but not in the reverse direction. Mediation analysis indicated that 36.5% (12.4-57.6%, P = 0.0499) of the effect from depression on type 2 diabetes was mediated by BMI. GWAS of type 2 diabetes and depressive symptoms did not identify shared loci. MP-GWAS identified seven shared loci mapped to TCF7L2, CDKAL1, IGF2BP2, SPRY2, CCND2-AS1, IRS1, CDKN2B-AS1. MDD has not brought any significant association in either GWAS or MP-GWAS. Most MP-GWAS loci had an eQTL, including single nucleotide polymorphisms implicating the cell cycle gene CCND2 in pancreatic islets and brain and the insulin signaling gene IRS1 in adipose tissue, suggesting a multitissue and pleiotropic underlying mechanism.
conclusionsOur 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.
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