PWAS: Proteome-wide association study - Linking genes and phenotypes by functional variation in proteins

Nadav Brandes*, Nathan Linial, Michal Linial*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

We introduce Proteome-Wide Association Study (PWAS), a new method for detecting gene-phenotype associations mediated by protein function alterations. PWAS aggregates the signal of all variants jointly affecting a protein-coding gene and assesses their overall impact on the protein's function using machine learning and probabilistic models. Subsequently, it tests whether the gene exhibits functional variability between individuals that correlates with the phenotype of interest. PWAS can capture complex modes of heritability, including recessive inheritance. A comparison with GWAS and other existing methods proves its capacity to recover causal protein-coding genes and highlight new associations. PWAS is available as a command-line tool.

Original languageAmerican English
Article number173
JournalGenome Biology
Volume21
Issue number1
DOIs
StatePublished - 14 Jul 2020

Bibliographical note

Publisher Copyright:
© 2020 The Author(s).

Keywords

  • GWAS
  • Machine learning
  • Protein annotations
  • Protein function
  • Recessive heritability
  • UK Biobank

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