ArticleGenome medicine2025
Distinct patterns of genetic overlap among multimorbidities revealed with trivariate MiXeR.
Article in Genome medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Mapping genetic convergence across brain structure, mental health, and cardiometabolic disease.Communications medicine · 2026Article
- Evidence for overlapping genetic architecture between lifestyle factors and severe mental disorders with different patterns across diagnoses.EBioMedicine · 2026Article
- Post-Stroke Depression Is Associated With Shared Neurodevelopmental Risk and Circuit Disruption.Brain and behavior · 2026Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
backgroundMultimorbidities are a global health challenge. Accumulating evidence indicates that overlapping genetic architectures underlie comorbid complex human traits and disorders. This can be quantified for a pair of phenotypes using various techniques. Still, the pattern of genetic overlap between three distinct complex phenotypes, which is important for understanding multimorbidities, has not been possible to quantify.
methodsHere, we present and validate the novel trivariate MiXeR tool, which disentangles the pattern of genetic overlap between three complex phenotypes using summary statistics from genome-wide association studies. Our simulations show that trivariate MiXeR can reliably reconstruct different patterns of genetic overlap and estimate the proportions of genetic overlap between three phenotypes.
resultsWe found substantial genetic overlap between gastro-intestinal and brain diseases supporting a genetic basis of the gut-brain axis-the pattern consistent with pairwise analysis. However, the pattern of genetic overlap between three diverse cardiometabolic and renal health indicators and three immune-linked disorders revealed a much larger genomic component shared between all phenotypes than expected from separate pairwise analyses. This suggests the existence of core pathways underlying distinct but related chronic conditions.
conclusionsOverall, trivariate MiXeR offers a novel and efficient tool for investigating patterns of genetic overlap among three complex phenotypes. This contributes to a better understanding of genetic relationships between complex traits and disorders, potentially providing new insights into the mechanisms underlying common multimorbidities. Trivariate MiXeR is freely available at https://github.com/precimed/mix3r .
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