Weill Cornell Medicine-Qatar (WCM-Q) researchers, working alongside peers from Sidra Medicine and Weill Cornell Medicine in New York, have made important new discoveries about genetic variations that affect human metabolism. This breakthrough could eventually help make diagnoses and treatments more effective.
The researchers analysed the genetic material and metabolism of 1,000 Qatari subjects to identify the link between them. While similar research has previously been carried out in European populations, this is the first time that such a large study of this kind has focused on an Arab population.
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The study, published in the leading scientific journal Nature Communications, sheds light on the role of genetic differences between people and their ability to metabolise certain molecules from food. Some of these genetic differences may explain why people have different risks of developing metabolic disorders, such as diabetes and cardiovascular disease.
The research established a high-quality data resource that will aid the diagnosis of inherited diseases among Qatari and other Arab populations. It will also help physicians identify targets for personalised treatments tailored to the individual genetic and metabolic profiles of patients.
The paper, titled ‘Whole-exome Sequencing Identifies Common and Rare Variant Metabolic QTLs in a Middle Eastern Population’ is authored by two experts: Dr Noha A Yousri, Assistant Professor of Genetic Medicine at WCM-Q, and Dr Khalid Fakhro, Director of Human Genetics at Sidra Medicine and also an Assistant Professor of Genetic Medicine at WCM-Q.
Dr Yousri said that while previous studies of this type – known as Metabolomics Genome Wide Association Studies (mGWAS) – have been conducted in Caucasian populations, none had looked at the Middle Eastern populations.
Our motivation was to make a similar study for Qataris to understand how genetic variations affect metabolite levels in both health and disease states in this population. However, the use of an enhanced technology – whole exome sequencing – facilitated studying the effect of functional variants, in particular, on moderating metabolic pathways.’
She said that the study will benefit the whole region as it will eventually allow prediction for any likelihood that individuals will develop certain diseases. It could also point the way towards more effective personalised medicine.
The researchers used a technique called Whole-Exome Sequencing (WES) to analyse the exome – the part of the genome that contains all of the protein-coding genes. They then used a technique called high-resolution metabolomics profiling to map the metabolic processes taking place in each individual.
In total, 1,303 metabolites were analysed. The two datasets were then compared using high-performance computers to pinpoint associations between metabolic disorders and genetic variants in particular positions on the chromosome, known as ‘loci’. In total, the study discovered 21 common genetic loci and 12 rare loci, 45 percent of which were completely new discoveries, presumably specific to Qatar.
The study was supported by the Biomedical Research Programme at WCM-Q, with funding from Qatar Foundation. It was also supported by Qatar National Research Fund.
For updates and more information about the research programme at WCM-Q, visit qatar-weill.cornell.edu.