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Table 1 Selected examples of published associations with hypothesis-free testing of metabolite ratios

From: On the hypothesis-free testing of metabolite ratios in genome-wide and metabolome-wide association studies

Metabolite ratio





Diabetic (db/db) versus wild type mice

Increased beta-oxidation in diabetic mice

Altmaier et al., Endocrinology, 2008

PC aa C36:3/PC aa C36:4

FADS1 genotype

Genetic variance in delta-5 fatty acid desaturation

Gieger et al., PLoS Genetics, 2008

PC aa Cx:y/PC ae Cx:y


Reduced or lack of activity of the enzyme alkyl-DHAP in smokers

Wang-Sattler et al., PLoS One, 2008

PC aa C40:3/PC aa C42:5

ELOVL2 genotype

Genetic variance in elongation of fatty acids

Illig et al., Nature Genetics, 2010

Medium chain fatty acids / long chain fatty acids

Diabetes state

Perturbed lipid metabolism associated with diabetes

Suhre et al., PLoS One, 2010

PC aa C40:5/PC aa C40:6

Self-reported nutritional intake of polyunsaturated fatty acids

Confirmation of questionnaire based life-style parameters

Altmaier et al., Eur. J. Endocrinology, 2011

Ratios between phospholipids with lipid side chains from the C16:0, C16:1, C18:0, C18:1 pool and C20:3, C20:4, C22:4 PUFAs

Plasma, tissue (mouse) and cell lines (human) treated with FABP4 inhibitor

Molecular inhibition of FABP4 activity

Suhre et al., J Biomol Screen, 2011

Formate/ acetate in human urine

NAT2 genotype

Genetic variance in N-acetylase activity

Suhre et al., Nature Genetics, 2011

Ratio between phosphorylated and unphosphorylated fibrinogen peptides

ABO, ALPL, and FUT2 genotypes

Genetic variance in fibrinogen phosphorylation

Suhre et al., Nature, 2011

  1. In all studies pairs of metabolites were identified by a high increase in the strength of association when ratios were used. Note that all of these metabolite pairs are found to be biochemically related to the concrete biological questions of these studies (Interpretation). However, they were singled out from the large number of all possible metabolite pair combinations on the basis of the p-gain without any prior hypotheses.