Polygenic threat assessments from multipurpose data should improve IBD predictions

Polygenic threat assessments from multipurpose data should improve IBD predictions


  • Post By : Kumar Jeetendra
  • Source: Sinai Mountain Health System
  • Date: December 25, 2020

Using genetic data from nearly 30,000 individuals, Mount Sinai researchers collected hazard 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 research was published in Gastroenterology on December 24.

The researchers found that the polygenic risk results, built on data from associations of several populations in the multiethnic BioMe Biobank on Mount Sinai, maximized IBD predictions for each population from the biobank. BioMe is a systemic experiment on Mount Sinai that revolutionizes the diagnosis and classification of diseases according to the molecular profile of an individual.

The ability to accurately predict the risk of genetic disease in individuals through ancestors is a crucial pathway that can positively impact patient outcomes, as early interventions and even preventive measures are considered and developed. 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. “

Judy H. Cho, Ph.D. Med., Atudy Senior Author, Dean of Translational Genetics and Director of the Institute of Personalized Medicine Charles Bronfman, Icahn School of Medicine, Mount Sinai

The study found that the risk scores calculated from incorporating the data significantly improved predictions among people of European, Jewish and Asian descent from Ashkenazi to BioMe, in addition to European individuals at the UK Bank, which contains medical and biological data on half a million people. aged 40 and 69 residing in the UK. The predictive power was lower for patients of African descent, probably due to significantly smaller data sets and significantly greater genetic diversity in populations of African descent.

These hazardous polygenic outcomes – which represent an estimate of the overall risk based on the amount of many, mostly common genetic variations of a person – were calculated using data on the association of IBD from a cohort of European, African American and Ashkenazi Jewish descent.

In addition, the researchers evaluated rare variations in IBD-associated genes with a very early onset in each population and found that African-American carriers of rare LRBA variants show decreased expression of both LRBA and CTLA-4 proteins. LRBA deficiency increases susceptibility to IBD and results in decreased expression of CTLA-4, which is the opposite of the common antimalarial drug chloroquine. Future studies to be performed by Cho Laboratory will focus on predicting which subsets of patients may 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, postdoctoral fellow in the Department of Genetics and Genomic Sciences at the Icahn School of Medicine on Mount Sinai.


Sinai Mountain Health System