Heat map of selected PheWAS associations.

<p>Associations are shown for each variant with each trait, for the set of all traits that had association with any -variant at 5% FDR. For each association, black circles are drawn with area proportional to the effect size point estimate (inner circle) and 95% upper confidence limit (outer circle), scaled relative to the maximum within each trait. The inner circle is colored according to the effect direction (blue to red) and significance (color scale according to association Z score, with corresponding q value cut-offs shown in the legend). Traits and [variants] are ordered using hierarchical clustering on Euclidean distances between columns [and rows] of the association Z score matrix.</p

Association and literature results.

<p>Summary of association statistics for study results and previously reported associations for Crohn’s disease, IBD, psoriasis, psoriatic arthritis and eczema.</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

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

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

Genome-Wide Significant SNPs from the Sex-Combined Multi-Ethnic Meta-Analysis.

<p>The novel loci identified using Multi-Ethnic Meta-analysis (that were not identified in the European only analysis) are listed in <b>bold</b>.</p>*<p>When possible, plausible biological candidate genes have been listed; otherwise, the closest gene is designated.</p>‡<p>Lead SNP is the SNP with the lowest <i>p</i>-value for each locus.</p>†<p>Positions are relative to Human Genome NCBI Build 36.</p>§<p>log₁₀ Bayes factor (BF) from the MANTRA analysis. A log₁₀ BF of 6 and higher was considered as a conservative threshold for genome-wide significance.</p>††<p>The posterior probability of heterogeneity between studies.</p>¶<p>EA: effect allele, NEA: non-effect allele.</p>¶¶<p>EAF: Frequency of effect allele in CEU, East Asian, and AA, populations respectively.</p

The Association of Lead Genome-Wide Significant SNPs for Adiponectin with mRNA Levels of Their Nearest Gene.

‡<p>Lead SNP is the SNP with the lowest <i>p</i>-value for each gene in gene expression data.</p>‡‡<p>Lead SNP is the SNP with the lowest <i>p</i>-value for each locus in meta-analysis from discovery phase.</p>¶<p>EA: Effect allele.</p>¶¶<p>EAF: Frequency of effect allele.</p>§<p>Betas are estimated expression levels of the genes.</p>*<p>P value for lead SNP is the SNP in gene expression data.</p>**<p>P value for lead SNP in meta-analysis from discovery phase.</p>$<p>r² LD between lead SNP from expression and lead SNP from meta-analysis.</p