Fig. 2: Discovery of pleiotropic variants and their relationship to disease.

a Manhattan plot of the output of the multivariate genome-wide association study (GWAS) on all 249 metabolites, with the observed -log10(p-value) for each variant shown on the y-axis. The x-axis shows the relative genomic location, grouped by chromosome, and the red dashed line indicates the genome-wide significance threshold of 5 × 10⁻⁸. The colour coding represents the number of genome-wide significant associations of each variant with metabolites at the univariate level, ranging from 0 (in black) to 214 (in red), illustrating the extent of pleiotropy. Loci with p < 1 × 10⁻³⁰⁰ have been annotated with mapped gene names. b heatmap showing 30 multivariate GWAS-identified loci with the highest number of Bonferroni-corrected significant associations with diseases, based on published GWAS. On the x-axis are the locus lead variants with mapped genes, and on the y-axis the categories of diseases as compiled by OpenTargets. The cell colouring indicates the -log10(p-value) of the variant-disease association, as indicated by the legend on the right.