The epigenome, 4D nucleome and next-generation neuropsychiatric pharmacogenomics

Abstract

The 4D nucleome has the potential to render challenges in neuropsychiatric pharmacogenomics more tractable. The epigenome roadmap consortium has demonstrated the critical role that noncoding regions of the human genome play in determination of human phenotype. Chromosome conformation capture methods have revealed the 4D organization of the nucleus, bringing interactions between distant regulatory elements into close spatial proximity in a periodic manner. These functional interactions have the potential to elucidate mechanisms of CNS drug response and side effects that previously have been unrecognized. This perspective assesses recent advances likely to reveal novel pharmacodynamic regulatory pathways in human brain, charting a future new avenue of pharmacogenomics research, using the spatial and temporal architecture of the human epigenome as its foundation.

Keywords: CNS; GWAS; allelic imbalance; biochronicity; candidate genes; chromatin interaction networks; genome-wide association studies; long noncoding RNAs; noncoding gene variants; pathway analysis; pharmacoepigenomics; psychotropic medications; super-resolution microscopy; transcription factors.