Multi-population risk outcomes could improve risk prediction for inflammatory bowel disease, the study reveals

Using genetic data from nearly 30,000 people, researchers at Mount Sinai built risk results from a combination of data sets representing different ancestral populations that improve risk prediction of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. The study was published in Gastroenterology December 24th.

The researchers found that polygenic risk scores, built on data from multi-population associations in the multiethnic BioMe Biobank in Sinai, maximized IBD predictions for each population in the biobank. BioMe is a systematic work on Mount Sinai that revolutionizes the diagnosis and classification of diseases according to the molecular profile of the patient. The study found that the risk results calculated from the data integration significantly improved predictions among people of European, Jewish and Asian descent Ashkenazi at BioMe, as well as among European individuals at the UK’s Great Bank, which contains biological and medical data on half a million people between ages 40 and 69 living in the UK. Predictive power was lower for patients of African descent, probably due to significantly smaller reference data sets and significantly greater genetic diversity within populations of African descent.

“The ability to accurately predict the risk of genetic disease in individuals through ancestors is a crucial pathway that can positively impact patient outcomes because early interventions and even preventive measures are considered and developed,” says the study’s senior author, Dr. Med., Judy H. Cho, Dean of Translational Genetics and Director of the Charles Bronfman Institute for Personalized Medicine at Icahn Medical School on Mount Sinai. “These findings support the need for greater genetic diversity, including more data on African American populations, to improve disease risk predictions and reduce health disparities for all populations.”

These polygenic risk outcomes – which represent an assessment of total risk based on the sum of many, mostly common genetic variants of an individual – were calculated using data on the association of IBD from the cohort with European, African American and Ashkenazi Jewish origins. In addition, the researchers evaluated rare variants in IBD-associated genes with a very early onset in each population and found that African-American carriers of unusual LRBA variables show decreased expression of both LRBA and CTLA-4 proteins. LRBA deficiency increases susceptibility to IBD and results in lower CTLA-4 expression, which can be reversed by the commonly prescribed antimalarial drug chloroquine. Future studies to be performed by the Cho laboratory will focus on predicting which subsets of patients could benefit from targeting this pathway.

“Because decreased expression of LRBA and CTLA-4 can lead to IBD, it is encouraging that chloroquine can partially recover expression,” says study author Dr. Kyle Gettler, a postdoctoral fellow in the Department of Genetics and Genomic Sciences at the Icahn School of Medicine on Mount Sinai.


The study was supported by grants R01 DK123530-01, 5 U24 DK062429-18, 5 U01 DK062422-18, R01 DK106593, and the Helmsley Charitable Trust (VEO-IBD Consortium).

About the health system of Mount Sinai

Mount Sinai Health System is the largest academic medical system in New York City, encompassing eight hospitals, a leading medical school, and an extensive network of outpatient practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and shared clinical leadership, ensuring that we provide the highest quality care – from prevention to treatment of the most severe and complex human diseases. The healthcare system includes more than 7,200 physicians and features a robust and ever-growing network of multispecialist services, including more than 400 outpatient locations in five New York City, Westchester, and Long Island counties. Mount Sinai Hospital is ranked 14th on the U.S. News & World Report’s list of honors Top 20 Best Hospitals in the Country and Icahn Medical School as one of the top 20 medical schools in the country. Mount Sinai health system hospitals are consistently regionally ranked by specialty, and our physicians are among 1% of all physicians nationwide according to US News & World Report.

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