Non-additive effects of schizophrenia risk genes reflect convergent downstream function.

ABSTRACT: Genetic studies of schizophrenia (SCZ) reveal a complex polygenic risk architecture comprised of hundreds of risk variants, the majority of which are common in the population at-large and confer only modest increases in disorder risk. Precisely how genetic variants with individually small predicted effects on gene expression combine to yield substantial clinical impacts in aggregate is unclear. Towards this, we previously reported that the combinatorial perturbation of four SCZ risk genes ("eGenes", whose expression is regulated by common variants) resulted in gene expression changes that were not predicted by individual perturbations, being most non-additive among genes associated with synaptic function and SCZ risk. Now, across fifteen SCZ eGenes, we demonstrate that non-additive effects

SUBMITTER: Deans PM 

PROVIDER: S-EPMC10055596 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature