Using genetic data from nearly 30,000 people, Mount Sinai researchers have constructed risk scores from a combination of data representing specific ancestry numbers that improve risk prediction for inflammatory bowel disease (IBD). including Crohn’s disease and ulcerative colitis. The study was published in Gastroenterology on 24 December.
The researchers found that polygenic risk scores, constructed using association data from multiples in Mount Sinai’s multivariate BioMe Biobank, increased IBD prediction for all populations in the biobank. BioMe is a system-wide effort at Mount Sinai that reconstructs the diagnosis and classification of diseases according to the molecular image of the patient.
The study showed that risk scores calculated from data integration significantly improved prediction among people of European, Ashkenazi Jewish, and Hispanic ancestry in BioMe, as well as European individuals in Biobank UK, which contains biological and medical data of half a million people between the ages. 40 and 69 live in the UK. Predictive power was lower for patients of African ancestry, possibly due to much smaller reference information sets and much greater genetic diversity within populations of African descent.
The ability to accurately predict the risk of genetic disease in individuals over ancestry is an essential means that can have a positive impact on patient outcomes, as early interventions and even measures are being considered and developed. protection. These findings support the need for greater genetic diversity, including more data on African American populations, to promote disease risk prediction and reduce health disparities for all populations. “
Judy H. Cho, MD, Lead Author Atudy, Dean of Translational Genetics and Director of the Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine, Mount Sinai
These polygenic risk scores – representing an estimate of overall risk based on the sum of a person’s genetic differences, which were mostly common – were calculated using IBD association data from co -aces with a European, African and Ashkenazi Jewish background.
In addition, researchers evaluated rare mutations in early-onset IBD-related genes within each population and found that African American carriers of mutations abnormal LRBAs show less interpretation of both LRBA and CTLA-4 proteins. LRBA deficiency increases susceptibility to IBD and leads to lower CTLA-4 sensitivity, which can be reversed with the commonly prescribed antimalarial drug chloroquine. Future studies by Cho Laboratory will focus on predicting which subsets of patients might benefit from targeting this pathway.
“Given that depleted LRBA and CTLA-4 expression can lower IBD, it is encouraging that chloroquine is able to regain emotion,” says first study author Kyle Gettler, PhD, graduate in the Department of Genetics and Genomic Sciences at Icahn School of Medicine at Mount Sinai.
Source:
Mount Sinai Health System