ArticleBMJ open gastroenterology2024
Multiancestry transferability of a polygenic risk score for diverticulitis.
Article in BMJ open gastroenterology, 2024. 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
objectivePolygenic risk scores (PRS) for diverticular disease must be evaluated in diverse cohorts. We sought to explore shared genetic predisposition across the phenome and to assess risk stratification in individuals genetically similar to European, African and Admixed-American reference samples.
methodsA 44-variant PRS was applied to the
resultsThe cohort comprised 181 719 individuals for PheWAS and 50 037 for risk modelling. PheWAS identified associations with diverticular disease, connective tissue disease and hernias. Across ancestry groups, one SD PRS increase was consistently associated with greater odds of severe (range of ORs (95% CI) 1.60 (1.27 to 2.02) to 1.86 (1.42 to 2.42)) and of symptomatic diverticulitis ((95% CI) 1.27 (1.10 to 1.46) to 1.66 (1.55 to 1.79)) relative to controls. European models achieved the highest AUROC and Nagelkerke's R
conclusionAssociations between a diverticular disease PRS and severe presentations persisted in diverse cohorts when controlling for known risk factors. Relative improvements in model performance were observed, but absolute change magnitudes were modest.
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