| Title: | Systematic discovery of gene-environment interactions underlying the human plasma proteome in UK Biobank |
| Journal: | Nature Communications |
| Published: | 26 Aug 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39187491/ |
| DOI: | https://doi.org/10.1038/s41467-024-51744-5 |
Publication 13086
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Abstract
Understanding how gene-environment interactions (GEIs) influence the circulating proteome could aid in biomarker discovery and validation. The presence of GEIs can be inferred from single nucleotide polymorphisms that associate with phenotypic variability - termed variance quantitative trait loci (vQTLs). Here, vQTL association studies are performed on plasma levels of 1463 proteins in 52,363 UK Biobank participants. A set of 677 independent vQTLs are identified across 568 proteins. They include 67 variants that lack conventional additive main effects on protein levels. Over 1100 GEIs are identified between 101 proteins and 153 environmental exposures. GEI analyses uncover possible mechanisms that explain why 13/67 vQTL-only sites lack corresponding main effects. Additional analyses also highlight how age, sex, epistatic interactions and statistical artefacts may underscore associations between genetic variation and variance heterogeneity. This study establishes the most comprehensive database yet of vQTLs and GEIs for the human proteome.</p>
16 Keywords
- Adult
- Aged
- Biological Specimen Banks
- Biomarkers
- Blood Proteins
- Female
- Gene-Environment Interaction
- Genome-Wide Association Study
- Humans
- Male
- Middle Aged
- Polymorphism, Single Nucleotide
- Proteome
- Quantitative Trait Loci
- UK Biobank
- United Kingdom
11 Authors
- Robert F. Hillary
- Danni A. Gadd
- Zhana Kuncheva
- Tasos Mangelis
- Tinchi Lin
- Kyle Ferber
- Helen McLaughlin
- Heiko Runz
- Riccardo E. Marioni
- Christopher N. Foley
- Benjamin B. Sun
6 Applications
| Application ID | Title |
|---|---|
| 20361 | Comprehensive Phenotype-wide Association Studies (PheWAS)for Genetic Tool Variants relevant to GSK Drug Targets |
| 26041 | Large-Scale Sequencing in the UK Biobank to Facilitate Gene Discovery, Genome Sciences, and Precision Medicine |
| 44257 | Survey of Genetic Factors Affecting Disease Risk and Progression. |
| 53639 | Genetics of the comorbidities of cardiometabolic diseases |
| 65851 | Large-scale proteomic profiling to facilitate genetics-guided drug discovery and precision medicine: The UK Biobank - Pharma Proteomics Project (UKB-PPP) |
| 69804 | Large-scale whole genome sequencing of the UK Biobank cohort to generate and evaluate therapeutic hypotheses regarding targets, biomarkers and pathways implicated in disease |
Enabling scientific discoveries that improve human health