A genome-wide metabolic QTL analysis in Europeans implicates two loci shaped by recent positive selection

We have performed a metabolite quantitative trait locus (mQTL) study of the (1)H nuclear magnetic resonance spectroscopy ((1)H NMR) metabolome in humans, building on recent targeted knowledge of genetic drivers of metabolic regulation. Urine and plasma samples were collected from two cohorts of indi...

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Veröffentlicht in:	PLoS genetics 2011-09, Vol.7 (9), p.e1002270-e1002270
Hauptverfasser:	Nicholson, George, Rantalainen, Mattias, Li, Jia V, Maher, Anthony D, Malmodin, Daniel, Ahmadi, Kourosh R, Faber, Johan H, Barrett, Amy, Min, Josine L, Rayner, N William, Toft, Henrik, Krestyaninova, Maria, Viksna, Juris, Neogi, Sudeshna Guha, Dumas, Marc-Emmanuel, Sarkans, Ugis, Donnelly, Peter, Illig, Thomas, Adamski, Jerzy, Suhre, Karsten, Allen, Maxine, Zondervan, Krina T, Spector, Tim D, Nicholson, Jeremy K, Lindon, John C, Baunsgaard, Dorrit, Holmes, Elaine, McCarthy, Mark I, Holmes, Chris C
Format:	Artikel
Sprache:	eng
Schlagworte:	Acetyltransferases - genetics Acetyltransferases - metabolism Biology Chemistry Dimethylamines - blood Dimethylamines - metabolism Female Gene loci Genetics Genome-Wide Association Study Genomics Haplotypes Humans Isobutyrates - metabolism Isobutyrates - urine Magnetic Resonance Spectroscopy Mathematics Medicine Metabolic Networks and Pathways - genetics Metabolites Metabolome - genetics Methylamines - metabolism Methylamines - urine NMR Nuclear magnetic resonance Nuclear magnetic resonance spectroscopy Pathology Patologi Polymorphism, Single Nucleotide Quantitative trait loci Quantitative Trait Loci - genetics Selection, Genetic Single nucleotide polymorphisms
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Zusammenfassung:	We have performed a metabolite quantitative trait locus (mQTL) study of the (1)H nuclear magnetic resonance spectroscopy ((1)H NMR) metabolome in humans, building on recent targeted knowledge of genetic drivers of metabolic regulation. Urine and plasma samples were collected from two cohorts of individuals of European descent, with one cohort comprised of female twins donating samples longitudinally. Sample metabolite concentrations were quantified by (1)H NMR and tested for association with genome-wide single-nucleotide polymorphisms (SNPs). Four metabolites' concentrations exhibited significant, replicable association with SNP variation (8.6×10(-11)
ISSN:	1553-7404 1553-7390 1553-7404
DOI:	10.1371/journal.pgen.1002270