Research Highlights : Precision Medicine in Arab, Middle East and North Africa

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).

Landscape of warfarin and clopidogrel pharmacogenetic variants in Qatari population from whole exome datasets

posted Jul 5, 2017, 6:54 AM by Vinod Scaria   [ updated Jul 5, 2017, 6:58 AM ]

Pharmacogenetic landscapes of commonly used antiplatelet drugs, warfarin and clopidogrel have been studied in-depth in many countries. However, there is a paucity of data to understand their patterns in the Arab populations. We analyzed the whole exome sequencing datasets of 100 Qatar individuals available in public domain with this perspective. We characterized the allelic distribution of variants routinely tested for warfarin and clopidogrel. We additionally evaluated the population stratification and its effect on allele frequency distribution. Our analysis points to ethnic differences in the frequency distribution even for the small population studied. This is one of the first and most comprehensive pharmacogenetic maps of variants associated with warfarin and clopidogrel for an Arab population, which can help tailor the drug dosage to the population.

Sivadas A, Sharma P, Scaria V
Landscape of warfarin and clopidogrel pharmacogenetic variants in Qatari population from whole exome datasets
Pharmacogenomics (2016) Accepted doi: 10.2217/pgs-2016-0130

Genetic epidemiology of Familial Mediterranean Fever through integrative analysis of whole genome and exome sequences from Middle East and North Africa

posted Jun 13, 2017, 8:43 AM by Vinod Scaria   [ updated Jun 13, 2017, 8:44 AM ]

Familial Mediterranean fever (FMF), an autosomal recessive and rare autoinflammatory disease is caused by genetic mutations in the MEFV gene and is highly prevalent in the Mediterranean basin. Though the carrier frequency of specific disease variants in the MEFV gene has been reported from isolated studies, a comprehensive view of variants in the Mediterranean region has not been possible due to paucity of data. The recent availability of whole-genome and whole-exome datasets prompted us to study the genetic epidemiology of MEFV variants in the region. We assembled data from five datasets encompassing whole-genome and whole-exome datasets for 2115 individuals from multiple subpopulations in the region and also created a compendium for MEFV genetic variants, which were further systematically annotated as per the ACMG guidelines. Our analysis points to significant differences in allele frequencies in the subpopulations, and the carrier frequency for MEFV genetic variants in the population to be about 8%. The MEFV gene appears to be under natural selection from our analysis. To the best of our knowledge, this is the most comprehensive study and analysis of population epidemiology of MEFV gene variants in the Middle East and North African populations.

Clinical Genetics (2017) Accepted
DOI: 10.1111/cge.13070

Integrating genetic variants in Middle East, Arab and North African populations towards Precision Medicine

posted Dec 3, 2016, 11:40 PM by Vinod Scaria   [ updated May 20, 2017, 7:01 AM ]

Precision Medicine is a new concept and an emerging model of healthcare where the genetic makeup and its interaction with the environment in incorporated towards enabling prevention, precise diagnosis and prognostication as well as precise treatment and management of a disease or condition.

A number of diseases are quite prevalent in the Arab world. A large part of this is attributed to the widespread practice and norm of consanguinity in the region. Understanding the genetic characteristics of many such diseases would provide the much necessary knowledge to build an effective healthcare system where early screening, early diagnosis and effective management cans significantly reduce the morbidity and mortality due to such diseases.
Middle East and North Africa (MENA) encompass very unique populations, with rich history and encompasses a characteristic ethnic, linguistic and genetic diversity. The genetic diversity of MENA region has been largely unknown. The recent availability of whole exome and whole genome sequences from the region has made it possible to collect population specific allele frequencies. The integration of datasets from this region would provide insights into the landscape of genetic variants in this region.

We have systematically integrated genetic variants from multiple data-sets available from this region to create a compendium of over 26 million genetic variations including over 6 million novel genetic variants.

To the best of our knowledge, al mena is a first and most comprehensive repertoire of genetic variations from the Arab, Middle Eastern and North African region. We hope al mena would be the first step to enable Precision Medicine in the region.

Koshy R, Ranawat A, Scaria V.
al mena - a comprehensive resource of human genetic variants integrating genomes and exomes from Arab, Middle Eastern and North African populations.
(in communication) 2017
Resource can be accessed at URL
The resource is exclusively for Academic use. 

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

In Media

Qatar exome study: An advancement in precision medicine
Louise Sarant in Nature Middle East

Scientists have used information from the whole-exome sequencing of 100 Qataris to create a comprehensive map of pharmacogenetic variants associated with two anticoagulants. [read more]

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