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

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8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number333
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Fingerprint

Exome
sequencing
Quantitative Trait Loci
loci
Metabolites
Metabolomics
Population
Medicine
Genes
Middle East
Precision Medicine
genome
metabolites
Genome-Wide Association Study
Proteins
medicine
Individuality
Pharmacology
proteins
high resolution

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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title = "Whole-exome sequencing identifies common and rare variant metabolic QTLs in a Middle Eastern population",
abstract = "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.",
author = "Noha Yousri and Fakhro, {Khalid Adnan Mohamed A.} and Amal Robay and Rodriguez-Flores, {Juan L.} and Mohney, {Robert P.} and Abbar, {Hassina Z.} and Tala Odeh and Sara Abdulkader and Eman Aldous and Gaurav Thareja and Manish Kumar and Alya Al-Shakaki and Omar Chidiac and {Ali Mohamoud}, Yasmin and Mezey, {Jason G.} and Joel Malek and Ronald Crystal and Karsten Suhre",
year = "2018",
month = "12",
day = "1",
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journal = "Nature Communications",
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AU - Yousri, Noha

AU - Fakhro, Khalid Adnan Mohamed A.

AU - Robay, Amal

AU - Rodriguez-Flores, Juan L.

AU - Mohney, Robert P.

AU - Abbar, Hassina Z.

AU - Odeh, Tala

AU - Abdulkader, Sara

AU - Aldous, Eman

AU - Thareja, Gaurav

AU - Kumar, Manish

AU - Al-Shakaki, Alya

AU - Chidiac, Omar

AU - Ali Mohamoud, Yasmin

AU - Mezey, Jason G.

AU - Malek, Joel

AU - Crystal, Ronald

AU - Suhre, Karsten

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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