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Reconstructing the blood metabolome and genotype using long-range chromatin interactions
Tayaza Fadason1,2, William Schierding1,2, Nikolai Kolbenev3
1The Liggins Institute, The University of Auckland, Auckland, New Zealand.
Metabolism Open
|August 20, 2020
Summary
Single nucleotide polymorphisms (SNPs) linked to blood metabolite levels were studied. We identified 577 genes in 48 tissues regulated by these SNPs, improving understanding of metabolic regulation.
Area of Science:
- Genomics
- Metabolomics
- Systems Biology
Background:
- Maintaining stable blood metabolite levels is vital for organismal health.
- Single nucleotide polymorphisms (SNPs) are linked to altered blood metabolite levels.
- The functional impact of metabolite-associated SNPs in non-coding regions remains largely unknown.
Purpose of the Study:
- To identify genes and tissues associated with blood metabolite level changes.
- To characterize genome-wide spatial regulatory interactions involving metabolite-associated SNPs.
Main Methods:
- Systematic integration of chromatin interaction (Hi-C) data.
- Utilized expression quantitative trait loci (eQTL) analysis.
- Incorporated gene ontology, drug interaction, and literature data for 145 blood metabolite-associated SNPs.
Main Results:
- Identified 577 genes regulated by 130 metabolite-associated SNPs across 48 human tissues.
- Affected genes are enriched in metabolism, enzyme activity, plasma proteins, disease development, and drug target categories.
- Regulatory interactions in non-target tissues influence blood metabolite levels.
Conclusions:
- Spatial SNP-gene-metabolite associations were identified.
- Expanded the list of genes and tissues affected by metabolite-associated SNPs.
- Enhanced understanding of molecular mechanisms behind abnormal blood metabolite levels.
