Reconstructing the blood metabolome and genotype using long-range chromatin interactions

Abstract

The mechanisms of metabolism comprise a large number of biochemical pathways with a myriad of poorly characterised genetic influences. In this study, we perform a systematic integration of chromatin interaction (Hi-C), expression quantitative trait loci (eQTL), gene ontology, drug interaction, and literature-supported connections to deconvolute the genetic regulatory influences of 145 blood metabolite-associated single nucleotide polymorphisms (SNPs). We identify 577 genes that are regulated via chromatin looping to 130 distal and proximal SNPs across 48 different human tissues. The affected genes are enriched in categories that include metabolism, enzymes, plasma proteins, disease development, and potential drug targets. These novel SNP-gene-metabolite associations are a valuable resource for understanding the molecular mechanisms guiding pathologic metabolite levels in human tissues, and for further investigation into disease diagnosis and therapy.