Estimating the mutational load for cardiovascular diseases in Pakistani population

Area of Science:

• Genetics
• Cardiovascular Diseases
• Population Genetics

Background:

• Genetic variant frequencies differ across populations due to evolutionary factors.
• Cardiovascular diseases (CVDs) have diverse genetic underpinnings influenced by population-specific variants.

Purpose of the Study:

• To identify and prioritize deleterious genetic variants associated with common, Mendelian, and congenital cardiovascular diseases (CVDs) in the Pakistani population.
• To compare allele frequencies of these variants with other global populations.

Main Methods:

• Utilized genome/exome sequencing data from Pakistani individuals (1000 Genomes Project - PJL) and South Asian data (ExAC).
• Applied variant annotation tools: Combined Annotation Dependent Depletion (CADD), ANNOVAR, and Variant Effect Predictor (VEP).
• Filtered variants using ClinVar for pathogenicity and compared derived allele frequencies (DAF).

Main Results:

• Identified 561 potentially detrimental variants from PJL data and 7374 from ExAC South Asian data.
• Found 5 pathogenic/likely pathogenic variants in PJL and 154 in ExAC South Asian data for CVDs.
• Observed significantly higher DAF for many prioritized variants in Pakistanis compared to other populations.

Conclusions:

• The Pakistani population harbors unique deleterious genetic variants contributing to CVDs.
• Population-specific genetic screening is crucial for understanding and managing CVDs effectively.
• Hypertension, atherosclerosis, heart failure, cardiomyopathies, and cardiac arrhythmias are notably associated with high-frequency deleterious variants in this population.