Examining the biological mechanisms of human mental disorders resulting from gene-environment interdependence using novel functional genomic approaches

Neurobiol Dis. 2023 Mar;178:106008. doi: 10.1016/j.nbd.2023.106008. Epub 2023 Jan 20.


We explore how functional genomics approaches that integrate datasets from human and non-human model systems can improve our understanding of the effect of gene-environment interplay on the risk for mental disorders. We start by briefly defining the G-E paradigm and its challenges and then discuss the different levels of regulation of gene expression and the corresponding data existing in humans (genome wide genotyping, transcriptomics, DNA methylation, chromatin modifications, chromosome conformational changes, non-coding RNAs, proteomics and metabolomics), discussing novel approaches to the application of these data in the study of the origins of mental health. Finally, we discuss the multilevel integration of diverse types of data. Advance in the use of functional genomics in the context of a G-E perspective improves the detection of vulnerabilities, informing the development of preventive and therapeutic interventions.

Keywords: Early adversity; Epigenetics; GWAS; Genes; Mental disorders; Polygenic scores; functional genomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Profiling
  • Genomics*
  • Humans
  • Mental Disorders* / genetics
  • Metabolomics
  • Proteomics / methods