Rxivist logo

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 (22.5x) whole-genome sequencing (WGS) in 1,328 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=1,605, 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 non-coding 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.

Download data

  • Downloaded 946 times
  • Download rankings, all-time:
    • Site-wide: 20,268
    • In genetics: 1,013
  • Year to date:
    • Site-wide: 58,997
  • Since beginning of last month:
    • Site-wide: 35,660

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News