Actionable genomic variants in 6045 participants from the Qatar Genome Program

Area of Science:

• Genomic Medicine
• Population Genomics
• Clinical Genetics

Background:

• Clinical DNA sequencing can reveal secondary findings unrelated to the initial genetic evaluation.
• The American College of Medical Genetics and Genomics (ACMG) recommends reporting variants in 59 specific genes.
• Existing data on secondary findings lack representation from Middle Eastern populations.

Purpose of the Study:

• To identify and analyze medically actionable variants within the 59 ACMG genes.
• To assess the prevalence of pathogenic variants in the Qatari population.
• To investigate phenotype-genotype associations for ACMG variants in the QGP cohort.

Main Methods:

• Whole-genome sequencing (WGS) data from 6045 participants in the Qatar Genome Program (QGP) were analyzed.
• Medically actionable variants in the 59 ACMG-recommended genes were identified.
• Phenotype data from QGP participants and clinical records were used for association studies.

Main Results:

• A total of 60 pathogenic or likely pathogenic variants were found in 25 ACMG genes among 141 individuals.
• 2.3% of the QGP participants carried at least one pathogenic/likely pathogenic variant in the 59 ACMG genes.
• Significant phenotype associations were identified for two variants: c.313+3A>C in LDLR and c.58C>T (p.Gln20*) in TPM1.

Conclusions:

• The study provides crucial data on the prevalence of medically actionable variants in the Arab and Middle Eastern populations.
• Genomic sequencing in diverse populations is essential for accurate genetic risk assessment.
• The findings support the integration of ACMG variant analysis into clinical practice for Middle Eastern cohorts.