Fig. 8: DPEP1 influences plasma levels of major digestive enzymes. | Nature Genetics

Fig. 8: DPEP1 influences plasma levels of major digestive enzymes.

From: Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine

Fig. 8: DPEP1 influences plasma levels of major digestive enzymes.

a, Schematic representation of the role of DPEP1, encoded by DPEP1, and several other genes in glutathione (GSH) metabolism, highlighting identified metabolites and genes. ABCC1, ATP-binding cassette subfamily C member 1; GGT1, γ-glutamyltransferase 1. b, DPEP1 transcript levels are particularly high in the small intestine (terminal ileum), pancreas, kidney and testis among GTEx version 8 samples (nsmall intestine, terminal ileum = 187, npancreas = 328, nkidney cortex = 85, ntestis = 361, nkidney medulla = 4, nothers = 9–803; Methods). The dark bars in the violin plots mark the 25th and 75th percentiles. c, Regional association plots of association patterns at the DPEP1 locus (linear regression). SNPs are plotted by position (build 38) versus −log10 (association P values) of plasma DPEP1 levels (top; conditional independent protein quantitative trait locus (pQTL) statistics with the index SNP rs258341), urine cysteinylglycine (middle; mQTL) and plasma levels of the digestive enzyme pancreatic triacylglycerol lipase (PNLIP) (bottom; conditional independent pQTL statistics with the index SNP rs1126464). The purple diamond highlights the index SNP for each association. SNPs are color coded to reflect their LD with this SNP (pairwise European-ancestry r2 values from the 1000 Genomes Project phase 3). Genes, exons and the direction of transcription from the University of California at Santa Cruz Genome Browser are depicted. Plots were generated using LocusZoom52. d, Network representation of metabolites with a DPEP1 mQTL as well as of all traits in the phenome-wide scan that are linked through positive colocalization for one of these. mQTLs are represented by the edge connecting the respective gene and metabolite, and all other edges are established through positive colocalization (PP H4 > 0.8), with color coding representing the phenotype category. Effect directions are indicated by the line type (solid, positive association; dashed, inverse association). CNS, central nervous system; NOS, not otherwise specified.

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