Whole-exome sequencing identifies common and rare variant metabolic QTLs in a Middle Eastern population

Metabolomics-genome-wide association studies (mGWAS) have uncovered many metabolic quantitative trait loci (mQTLs) influencing human metabolic individuality, though predominantly in European cohorts. By combining whole-exome sequencing with a high-resolution metabolomics profiling for a highly consa...

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Bibliographic Details
Published in:	Nature communications Vol. 9; no. 1; pp. 333 - 13
Main Authors:	Yousri, Noha A., Fakhro, Khalid A., Robay, Amal, Rodriguez-Flores, Juan L., Mohney, Robert P., Zeriri, Hassina, Odeh, Tala, Kader, Sara Abdul, Aldous, Eman K., Thareja, Gaurav, Kumar, Manish, Al-Shakaki, Alya, Chidiac, Omar M., Mohamoud, Yasmin A., Mezey, Jason G., Malek, Joel A., Crystal, Ronald G., Suhre, Karsten
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 23-01-2018 Nature Publishing Group Nature Portfolio
Subjects:	631/208/205/2138 639/638/45/320 Adult Arabs Chromosome Mapping Cohort Studies Consanguinity Exome Female Gene loci Genetic Variation Genome-wide association studies Genome-Wide Association Study Genomes Genotype Genotype & phenotype High-Throughput Nucleotide Sequencing Humanities and Social Sciences Humans Male Metabolism Metabolites Metabolome Metabolomics Middle Aged Middle East multidisciplinary Pharmacology Population studies Precision medicine Quantitative Trait Loci Science Science (multidisciplinary)
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Summary:	Metabolomics-genome-wide association studies (mGWAS) have uncovered many metabolic quantitative trait loci (mQTLs) influencing human metabolic individuality, though predominantly in European cohorts. By combining whole-exome sequencing with a high-resolution metabolomics profiling for a highly consanguineous Middle Eastern population, we discover 21 common variant and 12 functional rare variant mQTLs, of which 45% are novel altogether. We fine-map 10 common variant mQTLs to new metabolite ratio associations, and 11 common variant mQTLs to putative protein-altering variants. This is the first work to report common and rare variant mQTLs linked to diseases and/or pharmacological targets in a consanguineous Arab cohort, with wide implications for precision medicine in the Middle East. Blood metabolites are influenced by a combination of genetic and environmental factors. Here, Yousri and colleagues perform a whole-exome sequencing study in combination with a metabolomics analysis to identify metabolic quantitative trait loci in a Middle Eastern population.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-017-01972-9