Risk scores from multiethnic populations improve risk prediction for inflammatory bowel disease (IBD), according to a study published in Gastroenterology. Researchers examined the effects of common and rare IBD variants on disease prediction and pathophysiology using exomesequence and single-nucleotide polymorphism array data from 29,358 individuals in the multiethnic BioMe biobank. Polygenic risk scores (PRS) were calculated from European, African American, and Ashkenazi Jewish reference casecontrol studies; all three datasets were used to run a meta-genomewide association study. PRS were then combined to examine which combination of scores best predicted IBD status. For every population in BioMe, combining risk scores based on association data from distinct ancestral populations improved IBD prediction; among individuals of European ancestry in the UK Biobank, prediction was significantly improved. For non-Europeans, lower predictive power was observed, partly due to lower African IBD case-control reference sizes. Associations for two very early-onset IBD genes, ADAM17 and LRBA, were replicated, with high dominant model penetrance in BioMe. There was an association for autosomal, recessive LRBA risk alleles with severe, early-onset autoimmunity.

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