Incidental and clinically actionable genetic variants in 1005 whole exomes and genomes from Qatar

posted Mar 28, 2018, 10:08 PM by Vinod Scaria   [ updated Mar 28, 2018, 10:08 PM ]
Incidental findings in genomic data have been studied in great detail in the recent years, especially from population-scale data sets. However, little is known about the frequency of such findings in ethnic groups, specifically the Middle East, which were not previously covered in global sequencing studies. The availability of whole exome and genome data sets for a highly consanguineous Arab population from Qatar motivated us to explore the incidental findings in this population-scale data. The sequence data of 1005 Qatari individuals were systematically analyzed for incidental genetic variants in the 59 genes suggested by the American College of Medical Genetics and Genomics. We identified four genetic variants which were pathogenic or likely pathogenic. These variants occurred in six individuals, suggesting a frequency of 0.59% in the population, much lesser than that previously reported from European and African populations. Our analysis identified a variant in RYR1 gene associated with Malignant Hyperthermia that has significantly higher frequency in the population compared to global frequencies. Evaluation of the allele frequencies of these variants suggested enrichment in sub-populations, especially in individuals of Sub-Saharan African ancestry. The present study thereby provides the information on pathogenicity and frequency, which could aid in genomic medicine. To the best of our knowledge, this is the first comprehensive analysis of incidental genetic findings in any Arab population and suggests ethnic differences in incidental findings.

Jain, A., Gandhi, S., Koshy, R. et al.
Incidental and clinically actionable genetic variants in 1005 whole exomes and genomes from Qatar
Mol Genet Genomics (2018). https://doi.org/10.1007/s00438-018-1431-8