Premium
Genetics’ Piece of the PI: Inferring the Origin of Complex Traits and Diseases from Proteome‐Wide Protein–Protein Interaction Dynamics
Author(s) -
Gauthier Louis,
Stynen Bram,
Serohijos Adrian W. R.,
Michnick Stephen W.
Publication year - 2020
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.201900169
Subject(s) - biology , phenotype , genetic architecture , proteome , genetics , computational biology , genetic variation , quantitative trait locus , genetic variants , evolutionary biology , human genetics , gene , genotype
How do common and rare genetic polymorphisms contribute to quantitative traits or disease risk and progression? Multiple human traits have been extensively characterized at the genomic level, revealing their complex genetic architecture. However, it is difficult to resolve the mechanisms by which specific variants contribute to a phenotype. Recently, analyses of variant effects on molecular traits have uncovered intermediate mechanisms that link sequence variation to phenotypic changes. Yet, these methods only capture a fraction of genetic contributions to phenotype. Here, in reviewing the field, it is proposed that complex traits can be understood by characterizing the dynamics of biochemical networks within living cells, and that the effects of genetic variation can be captured on these networks by using protein–protein interaction (PPI) methodologies. This synergy between PPI methodologies and the genetics of complex traits opens new avenues to investigate the molecular etiology of human diseases and to facilitate their prevention or treatment.