Disclosures: Cho and Gettler report no relevant financial disclosures. Please see the full study for all other authors' relevant financial disclosures.
December 28, 2020
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More data needed on minority populations to enhance IBD risk scores

Disclosures: Cho and Gettler report no relevant financial disclosures. Please see the full study for all other authors' relevant financial disclosures.
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Polygenic risk scores compiled using data from a multi-ethnic biobank helped improve predictions for inflammatory bowel disease, according to study results.

However, researchers said there is a need for more genetic diversity, including more data from Black populations, to improve prediction of IBD risk and reduce health disparities.

“The ability to accurately predict genetic disease risk in individuals across ancestries is a critical avenue that may positively affect patient outcomes, as early interventions and even preventive measures are being considered and developed,” Judy H. Cho, MD, dean of translational genetics and director of The Charles Bronfman Institute for Personalized Medicine at the Icahn School of Medicine at Mount Sinai, said in a press release.

Researchers used data from Mount Sinai’s multi-ethnic BioMe biobank, comprising 29,358 individuals, to define the effects of common and rare variants of IBD on disease predictions and pathophysiology. They calculated polygenic risk scores from European, Black and Ashkenazi Jewish reference case-control studies and ran a meta-genome-wide association study using all three association datasets.

Then, investigators combined the polygenic risk scores to assess which combination of scores could predict IBD status in each cohort within the BioMe population. Finally, they explored which gene variants were associated with very early onset IBD (VEO-IBD).

Cho and colleagues found that combining risk scores based on association data improved IBD prediction for every population within BioMe, and significantly improved prediction among individuals with European ancestry in the United Kingdom biobank.

However, researchers found that the risk scores had lower predictive power among non-Europeans due to substantially smaller sizes of Black IBD case-control reference datasets, as well as greater genetic diversity within populations of African descent.

Researchers were also able to replicate associations between two VEO-IBD genes, ADAM17 and LRBA, which had high dominant model penetrance in BioMe.

Additionally, they found that individuals in the Black cohort who carried uncommon LRBA variants showed reduced expression of both proteins LRBA and CTLA-4 expression. Cho and colleagues are exploring which subsets of patients might benefit from targeting this pathway.

“Since lowered LRBA and CTLA-4 expression can lead to IBD, it’s encouraging that chloroquine is able to partially recover expression,” Kyle Gettler, PhD, postdoctoral fellow in the department of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai, said in the release.