| Title: | Whole-genome sequencing analysis of the cardiometabolic proteome |
| Journal: | Nature Communications |
| Published: | 10 Dec 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33303764/ |
| DOI: | https://doi.org/10.1038/s41467-020-20079-2 |
| URL: | https://www.nature.com/articles/s41467-020-20079-2.pdf |
Publication 9315
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Abstract
The human proteome is a crucial intermediate between complex diseases and their genetic and environmental components, and an important source of drug development targets and biomarkers. Here, we comprehensively assess the genetic architecture of 257 circulating protein biomarkers of cardiometabolic relevance through high-depth (22.5×) whole-genome sequencing (WGS) in 1328 individuals. We discover 131 independent sequence variant associations (P < 7.45 × 10−11) across the allele frequency spectrum, all of which replicate in an independent cohort (n = 1605, 18.4x WGS). We identify for the first time replicating evidence for rare-variant cis-acting protein quantitative trait loci for five genes, involving both coding and noncoding variation. We construct and validate polygenic scores that explain up to 45% of protein level variation. We find causal links between protein levels and disease risk, identifying high-value biomarkers and drug development targets.</p>
14 Authors
- Arthur Gilly
- Young-Chan Park
- Grace Png
- Andrei Barysenka
- Iris Fischer
- Thea Bjørnland
- Lorraine Southam
- Daniel Suveges
- Sonja Neumeyer
- N. William Rayner
- Emmanouil Tsafantakis
- Maria Karaleftheri
- George Dedoussis
- Eleftheria Zeggini
1 Application
| Application ID | Title |
|---|---|
| 10205 | Cardiometabolic trait genetics |
Enabling scientific discoveries that improve human health