Twenty-two identified and replicated loci and their overlap with associations to metabolic traits and clinical phenotypes.

a SNP with the strongest association to targeted metabolic traits (“lead SNP”)b SNP with the strongest association to non-targeted metabolic traitsc manually added to the list of most plausible candidate genes derived by evidence-based selectiond additional candidates match to other non-targeted traits that also associate with the lead SNPe results from GWAS (P −8)f mutations determined in clinical studiesFor each locus, we selected all variants that displayed genome-wide significant association signals to metabolic traits in the SHIP-0 cohort. We added their proxy variants in LD (r2 ≥ 0.8; based on 1000 genomes project data [50, 51]). These variant sets were used for the selection of candidate genes and the comparison with association results from other studies. Candidate genes: selection of genes based on variant evidence (genes hit or close-by, eQTL, potentially regulatory effects, or missense variants) (S3 Table). Genes with the highest evidence counts are listed. Genes with the most plausible biochemical relation to the associated trait are highlighted in bold typeface. Associated traits: Targeted/non-targeted metabolomics: traits that display genome-wide significant association signals in SHIP-0. The arrows indicate whether the trait increases (↗) or decreases (↘) per copy of the effect allele. For non-targeted traits, the most plausible metabolite candidates according to metabomatching are given. Other mGWAS in urine/blood: metabolic traits that were previously found to be associated with a locus variant. The arrows indicate the directionality of the effect for the reported effect allele (where available). Clinical phenotypes: overlap with variants found to be associated with clinical traits. Comment: Gene expression rates were taken from the Illumina Body Map 2.0 (S4 Table). Protein localizations were taken from the Human Protein Atlas (version 12) [52]. For genes linked to clinical traits, we provide OMIM or OrphaNet accession numbers if available. Functional match: Indicates which associations exhibit a sound biological link between gene function and the biochemical nature of the associated metabolite(s).Twenty-two identified and replicated loci and their overlap with associations to metabolic traits and clinical phenotypes.