ArticleJournal of the American Medical Informatics Association : JAMIA2026
Knowledge graph-augmented large language models for reconstructing life course risk pathways: a gestational diabetes mellitus-to-dementia case study.
Article in Journal of the American Medical Informatics Association : JAMIA, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesTo develop and evaluate a knowledge graph-augmented large language model (LLM) framework that synthesizes epidemiological evidence to infer life-course exposure-outcome pathways, using gestational diabetes mellitus (GDM) and dementia as a case study. MATERIALS AND
methodsWe constructed a causal knowledge graph by extracting empirical epidemiological associations from scientific literature, excluding hypothetical assertions. The graph was integrated with GPT-4 through four graph retrieval-augmented generation (GRAG) strategies to infer bridging variables between early-life exposure (GDM) and later-life outcome (dementia). Semantic triples served as structured inputs to support LLM reasoning. Each GRAG strategy was evaluated by human clinical experts and three LLM-based reviewers (GPT-4o, Llama 3-70B, and Gemini Advanced), assessing scientific reliability, novelty, and clinical relevance.
resultsThe GRAG strategy using a minimal set of abstracts specifically related to GDM-dementia bridging variables performed comparably to the strategy using broader sub-community abstracts, and both significantly outperformed approaches using the full GDM- or dementia-related corpus or baseline GPT-4 without external augmentation. The knowledge graph-augmented LLM identified 108 maternal candidate mediators, including validated risk factors such as chronic kidney disease and physical inactivity. The structured approach improved accuracy and reduced confabulation compared to standard LLM outputs. DISCUSSION: Our findings suggest that augmenting LLMs with epidemiological knowledge graphs enables effective reasoning over fragmented literature and supports the reconstruction of progressive risk pathways. Expert assessments revealed that LLMs may overestimate clinical relevance, highlighting the need for human-AI collaboration in interpretation and application.
conclusionIntegrating semantic epidemiological knowledge with LLMs via GRAG strategies provides a promising framework for life-course epidemiology, enabling early detection of modifiable risk factors and guiding variable selection in cohort study design.
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