ArticleGenome medicine2026
A multi-ancestry polygenic risk score for body mass index predicts longitudinal weight change.
Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- A multi-ancestry polygenic risk score for body mass index predicts longitudinal weight change.Genome medicine · 2026Article
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6 authors.
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Abstract
backgroundIdentifying individuals at risk for future weight gain is challenging, partly because associations with traditional clinical risk factors may be biased by confounding and reverse causation. Polygenic risk scores (PRS) provide a stable, lifelong measure of genetic predisposition to obesity. However, existing PRS have not been evaluated for their association with longitudinal weight change in adulthood and often lack generalizability across diverse genetic ancestry groups.
methodsWe conducted ancestry-specific genome-wide association study meta-analyses of body mass index (BMI) in populations of European, African or African American, Admixed American, East Asian, and South Asian ancestries and developed ancestry-specific PRS. A multi-ancestry polygenic risk score (MAPRS) was trained using ancestry-specific PRS in a model selection dataset (N = 39,685) from the All of Us Research Program (AoU). We evaluated the MAPRS in an independent AoU model evaluation dataset (N = 158,743) for BMI prediction and in a separate AoU test dataset (N = 78,219) with repeated measurements over 1.5-2.5 years for weight change prediction. The outcomes included change in BMI and ≥ 10% or ≥ 5% total body weight (TBW) gain. We further examined the relationship between MAPRS and 12 clinical risk factors commonly comorbid with obesity in relation to weight change.
resultsThe MAPRS captured 7.05% of the variance in measured BMI in the AoU model evaluation dataset and demonstrated improved generalizability across all non-European genetic ancestry groups. In the AoU test dataset, conditioned on baseline BMI at the second-to-last measurement, a one SD increase in MAPRS was associated with a 0.16 kg/m
conclusionsWe developed an MAPRS for BMI that represents a robust and generalizable risk factor for longitudinal weight gain in adulthood, providing a foundation for genetically informed risk stratification and earlier, more targeted obesity prevention strategies.
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