Akl Fahed, MD, MPH, a physician investigator in the Cardiovascular Research Center at Massachusetts General Hospital, is co-senior author of a new study in Nature Communications, Clinical Utility of Polygenic Scores for Cardiometabolic Disease in Arabs.

What Question Were You Investigating?

Can we use public databases to predict the risk of cardiometabolic disease in different ethnic populations based on genetic information?

With the growth of large genomic datasets, there is an important focus on their disproportionate enrichment for individuals of European ancestry and an urgent need for more non-European representation.

Arabs represent about 5% of the world population and are massively underrepresented in genomic studies worldwide, yet minimal efforts have been made to date to understand clinical utility of polygenic scores in this group.

What Methods Did You Use?

The study population included a disease cohort of 5,399 individuals referred for cardiac care at the King Faisal Specialist Hospital and Research Center and a population reference cohort of 1,107 indigenous Arabs not known to have cardiometabolic disease.

All participants provided blood samples for DNA extraction and genotyping.

Using the genomic and clinical data on this indigenous Arab population, we applied a pragmatic framework that leverages recent GWAS data and novel multi-ethnic computational methods to optimize polygenic scores for Arabs.

What Did You Find?

We optimized polygenic scores for 10 cardiometabolic traits, achieving a performance that is better than published European-derived scores and on par with performance of scores in European-ancestry individuals.

The cardiometabolic traits we optimized for include:

  • Coronary artery disease
  • Type 2 diabetes
  • Cardiomyopathy
  • LDL Cholesterol
  • HDL Cholesterol
  • Triglyceride
  • Systolic Blood Pressure
  • Diastolic Blood Pressure
  • Body Mass Index
  • Height

What are the Implications?

There are three key implications to our findings:

  1. We illustrate how public resources could be leveraged to study the clinical utility of polygenic scores in a subpopulation that is distinct geographically and genetically from global datasets and validate them in ancestry-matched individuals in a European biobank
  2. We show that polygenic risk is additive to conventional risk factors even in a population with very high prevalence of cardiometabolic disease
  3. We live in a global world where self-reported race and ethnicity is increasingly proving to be an inappropriate form of health-related measures. For example, we identified Arab-matched individuals in the UK Biobank who self-reported their race to be a variety of options yet have similar genetic ancestry to Arabs from Saudi Arabia and could benefit from optimized polygenic scores from this population rather than European polygenic scores.

Paper Cited:

Shim, I., Kuwahara, H., Chen, N., Hashem, M. O., AlAbdi, L., Abouelhoda, M., Won, H. H., Natarajan, P., Ellinor, P. T., Khera, A. V., Gao, X., Alkuraya, F. S., & Fahed, A. C. (2023). Clinical utility of polygenic scores for cardiometabolic disease in Arabs. Nature communications, 14(1), 6535. https://doi.org/10.1038/s41467-023-41985-1