ArticlePLoS genetics2023
A multivariate genome-wide association study of psycho-cardiometabolic multimorbidity.
Article in PLoS genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 2 of them syntheses that pooled it.
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Who cites it
9 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.
- Mapping Gastroesophageal Reflux Disease and Coronary Artery Disease: A Comprehensive Analysis of Multivariable Mendelian Randomization and Shared Genetic Etiology.Clinical cardiology · 2025Pooled it
- Lifestyle behaviours do not moderate the association between childhood maltreatment and comorbid depression and cardiometabolic disease in older adults: a meta-analysis.BMC medicine · 2025Pooled it
- 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
- Pleiotropy and disease interactors: the dual nature of genes linking ageing and ageing-related diseases.Biogerontology · 2026Article
- Combining polygenic risk scores to understand genetic liability to physical-mental health multimorbidity in UK Biobank.Human molecular genetics · 2026Article
- Childhood maltreatment and mental-physical multimorbidity: An analysis of Canadian survey data using entropy balancing.Canadian journal of public health = Revue canadienne de sante publique · 2026Article
- Genetic insights into number of long-term conditions and their relationship with lifespan.PloS one · 2026Article
- Linking the plasma proteome to genetics in individuals from continental Africa provides insights into type 2 diabetes pathogenesis.Nature genetics · 2026Article
- Transforming the cardiometabolic disease landscape: Multimodal AI-powered approaches in prevention and management.Cell metabolism · 2024Review
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Coronary artery disease (CAD), type 2 diabetes (T2D) and depression are among the leading causes of chronic morbidity and mortality worldwide. Epidemiological studies indicate a substantial degree of multimorbidity, which may be explained by shared genetic influences. However, research exploring the presence of pleiotropic variants and genes common to CAD, T2D and depression is lacking. The present study aimed to identify genetic variants with effects on cross-trait liability to psycho-cardiometabolic diseases. We used genomic structural equation modelling to perform a multivariate genome-wide association study of multimorbidity (Neffective = 562,507), using summary statistics from univariate genome-wide association studies for CAD, T2D and major depression. CAD was moderately genetically correlated with T2D (rg = 0.39, P = 2e-34) and weakly correlated with depression (rg = 0.13, P = 3e-6). Depression was weakly correlated with T2D (rg = 0.15, P = 4e-15). The latent multimorbidity factor explained the largest proportion of variance in T2D (45%), followed by CAD (35%) and depression (5%). We identified 11 independent SNPs associated with multimorbidity and 18 putative multimorbidity-associated genes. We observed enrichment in immune and inflammatory pathways. A greater polygenic risk score for multimorbidity in the UK Biobank (N = 306,734) was associated with the co-occurrence of CAD, T2D and depression (OR per standard deviation = 1.91, 95% CI = 1.74-2.10, relative to the healthy group), validating this latent multimorbidity factor. Mendelian randomization analyses suggested potentially causal effects of BMI, body fat percentage, LDL cholesterol, total cholesterol, fasting insulin, income, insomnia, and childhood maltreatment. These findings advance our understanding of multimorbidity suggesting common genetic pathways.
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