Metabomatching.

<p>Each subfigure compares the <i>CoLaus</i> pseudo-spectrum (bottom half) with the NMR spectrum (top half) of the most likely candidate for the associated metabolite. (A) rs37369 vs. 3-aminoisobutyrate. (B) rs2147896 in <i>PYROXD2</i> vs. trimethylamine (C) rs8101881 in <i>SLC7A9</i> vs. lysine (D) rs281408 in <i>FUT2</i> vs. fucose.</p

Allelic heterogeneity at the <i>AGXT2</i> locus.

<p>Abbreviations: <i>P_C, P_T</i> – P-values, <i>x_C, x_T</i> – multivariate effect sizes, <i>R²</i> – explained variance of full model, <i>R²_diff</i> – additional explained variance of full model compared to best single SNP association, <i>model P</i> – probability of observing same or equal <i>R²_diff</i> increase with the same stepwise model selection for 2,500 permuted phenotypes.</p

Local Manhattan plots.

<p>The Manhattan plots show combined −log(P-values) in the neighborhood of the most strongly associated SNP for (A) the <i>FUT2</i> with fucose association, and (B) the <i>SLC7A9</i> with lysine association.</p

Genome- and metabolome-wide analysis results, first stage.

<p>(A) Manhattan plot for feature 1.2025. (B) Genome- and metabolome-wide P-value heat map, showing associations with <i>P_C</i><5×10⁻⁸ in <i>CoLaus</i>. (C) Pseudo-spectrum for SNP rs37369, obtained by plotting the association P-values between rs37369 and all metabolic features.</p

Locus-metabolite associations.

<p>For every locus, the association results are listed for the strongest association, after meta-analysis, of a SNP in the locus with a feature (bold) of the metabolite. Abbreviations: Chr – chromosome, Position – chromosomal position in NCBI build 36, <i>x_C</i> – effect size in <i>CoLaus</i>, <i>x_T</i> – effect size in <i>TasteSensomics</i>, <i>x_m</i> – effect size after meta-analysis, <i>P_m</i> – P-value after meta-analysis.</p

Genotype-Metabotype-Phenotype associations.

<p>The two novel gene-metabolite associations of this study implicate SNPs that had previously been associated with disease-related phenotypes by the indicated publications: (A) Fucose–Crohn's disease–<i>FUT2</i> (rs492602), (B) Lysine–eGFR–<i>SLC7A9</i> (rs8101881). A link between the metabolite and the phenotype has been established for (A) based on a mouse model and for (B) by a direct correlation with the indicated significance and effect size. Abbreviations: OR refers to the odds ratio, <i>x</i> to the linear regression effect size, <i>P</i> to the corresponding P-value, and the <i>m</i>-index indicates values obtained in the combined <i>CoLaus</i> and <i>TasteSensomics</i> sample.</p