Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

Proteogenomic links to human metabolic diseases

Mine Koprulu, Julia Carrasco-Zanini, Eleanor Wheeler, Sam Lockhart, Nicola D. Kerrison, Nicholas J. Wareham, Maik Pietzner, Claudia Langenberg

Nature Metabolism · 2023

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Summary

This proteogenomic study examined the plasma proteome as an intermediate layer between genomic variation and disease phenotypes, integrating antibody-based proteomic measurements with genetic data in over 1,100 individuals. The work identified novel protein quantitative trait loci and demonstrated how genetic regulation of circulating proteins relates to metabolic disease risk, identifying specific candidates such as gastrin-releasing peptide for type 2 diabetes and TIMD4 for lipoprotein metabolism. The findings suggest that integrating complementary proteomic and genomic technologies can reveal new therapeutic targets for metabolic diseases.

Regional applicability

This study was conducted in the United Kingdom using British cohort data, making its findings directly applicable to UK clinical practice and public health policy. The identified protein biomarkers and genetic associations have potential relevance for UK healthcare strategies targeting type 2 diabetes and metabolic disease prevention and treatment.

Key measures

2,923 plasma proteins measured via antibody-based assays in 1,180 individuals; protein quantitative trait loci (pQTLs); genetic regulation patterns shared with 575 health outcomes; causal gene assignments; rare loss-of-function gene burden

Outcomes reported

The study identified 256 unreported protein quantitative trait loci (pQTLs) and demonstrated shared genetic regulation of 224 cis-pQTLs with 575 specific health outcomes, with particular focus on metabolic diseases including type 2 diabetes. It also improved causal gene assignment at 40% of overlapping risk loci and identified convergence between phenotypic consequences of cis-pQTLs and rare loss-of-function gene burden for 12 proteins.

Theme
Nutrition & health
Subject
Dietary patterns & chronic disease
Study type
Research
Study design
Observational cohort
Source type
Peer-reviewed study
Status
Published
Geography
United Kingdom
System type
Human clinical
DOI
10.1038/s42255-023-00753-7
Catalogue ID
SNmp6e6ypz-uu66kd

Topic tags

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