| Title: | Plasma proteome analyses in individuals of European and African ancestry identify cis-pQTLs and models for proteome-wide association studies |
| Journal: | Nature Genetics |
| Published: | 2 May 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35501419/ |
| DOI: | https://doi.org/10.1038/s41588-022-01051-w |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236177 |
| Citations: | 147 (125 in last 2 years) as of 8 Aug 2024 |
Publication 12385
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Abstract
Improved understanding of genetic regulation of the proteome can facilitate identification of the causal mechanisms for complex traits. We analyzed data on 4,657 plasma proteins from 7,213 European American (EA) and 1,871 African American (AA) individuals from the Atherosclerosis Risk in Communities study, and further replicated findings on 467 AA individuals from the African American Study of Kidney Disease and Hypertension study. Here, we identified 2,004 proteins in EA and 1,618 in AA, with most overlapping, which showed associations with common variants in cis-regions. Availability of AA samples led to smaller credible sets and notable number of population-specific cis-protein quantitative trait loci. Elastic Net produced powerful models for protein prediction in both populations. An application of proteome-wide association studies to serum urate and gout implicated several proteins, including IL1RN, revealing the promise of the drug anakinra to treat acute gout flares. Our study demonstrates the value of large and diverse ancestry study to investigate the genetic mechanisms of molecular phenotypes and their relationship with complex traits.</p>
6 Keywords
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Gout
- Humans
- Polymorphism, Single Nucleotide
- Proteome
11 Authors
- Jingning Zhang
- Diptavo Dutta
- Anna Köttgen
- Adrienne Tin
- Pascal Schlosser
- Morgan E. Grams
- Benjamin Harvey
- Bing Yu
- Eric Boerwinkle
- Josef Coresh
- Nilanjan Chatterjee
1 Application
| Application ID | Title |
|---|---|
| 17712 | Assesments of Joint Effect of Polygenic Disease-risk Scores and Modifiable Risk-factors on Major Chronic diseases and Mortality |
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