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

Abstract

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.

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Acknowledgements

Authors thank Dr. Srinivasan Ramachandran and Dr. Chetana Sachidanandan for suggestions which enriched the manuscript. Authors acknowledge funding from the Council of Scientific and Industrial Research (CSIR, India) through Grant BSC0212 (Wellness Genomics Project). AJ is a recipient of Junior Research Fellowship from Council of Scientific and Industrial research (CSIR, India). The funders had no role in the preparation of the manuscript or decision to submit. We acknowledge the researchers at Weill Cornell Medicine for sharing the genome and exome data sets without which this analysis was not possible.

Funding

This study was funded by Council of Scientific and Industrial Research (CSIR, India) through Grant BSC0212 (Wellness Genomics Project).

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Contributions

VS conceptualized and designed the study. AJ and SG performed the variant classification and data analysis. RK performed the re-analysis of annotations. AJ and RK compiled the results and interpreted with VS. All authors contributed to writing the manuscript.

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Correspondence to Vinod Scaria.

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Abhinav Jain declares that he has no conflict of interest. Shrey Gandhi declares that he has no conflict of interest. Remya Koshy declares that she has no conflict of interest. Vinod Scaria declares that he has no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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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 293, 919–929 (2018). https://doi.org/10.1007/s00438-018-1431-8

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Keywords

  • Arab
  • Genomics
  • Incidental findings
  • Malignant hyperthermia
  • Qatar