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

Nat Commun. 2018 Jan 23;9(1):333. doi: 10.1038/s41467-017-01972-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arabs*
  • Chromosome Mapping
  • Cohort Studies
  • Consanguinity
  • Exome*
  • Female
  • Genetic Variation
  • Genome-Wide Association Study*
  • Genotype
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Metabolome*
  • Middle Aged
  • Middle East
  • Quantitative Trait Loci*