A genome-wide metabolic QTL analysis in Europeans implicates two loci shaped by recent positive selection.
- Nicholson, G
- Rantalainen, M
- Li, JV
- Maher, AD
- Malmodin, D
- Ahmadi, KR
- Faber, JH
- Barrett, A
- Min, JL
- Rayner, NW
- Toft, H
- Krestyaninova, M
- Viksna, J
- Neogi, SG
- Dumas, ME
- Sarkans, U
- MolPAGE Consortium,
- Donnelly, Peter
- Illig, T
- Adamski, J
- Suhre, K
- Allen, Maxine
- Zondervan, KT
- Spector, TD
- Nicholson, JK
- Lindon, JC
- Baunsgaard, D
- Holmes, E
- McCarthy, MI
- Holmes, CC
DOIAbstract
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)<p<2.8×10(-23)). Three of these-trimethylamine, 3-amino-isobutyrate, and an N-acetylated co...
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