TY - JOUR TI - A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia AU - Skene, Nathan G AU - Roy, Marcia AU - Grant, Seth GN A2 - Flint, Jonathan VL - 6 PY - 2017 DA - 2017/09/12 SP - e17915 C1 - eLife 2017;6:e17915 DO - 10.7554/eLife.17915 UR - https://doi.org/10.7554/eLife.17915 AB - The genetic mechanisms regulating the brain and behaviour across the lifespan are poorly understood. We found that lifespan transcriptome trajectories describe a calendar of gene regulatory events in the brain of humans and mice. Transcriptome trajectories defined a sequence of gene expression changes in neuronal, glial and endothelial cell-types, which enabled prediction of age from tissue samples. A major lifespan landmark was the peak change in trajectories occurring in humans at 26 years and in mice at 5 months of age. This species-conserved peak was delayed in females and marked a reorganization of expression of synaptic and schizophrenia-susceptibility genes. The lifespan calendar predicted the characteristic age of onset in young adults and sex differences in schizophrenia. We propose a genomic program generates a lifespan calendar of gene regulation that times age-dependent molecular organization of the brain and mutations that interrupt the program in young adults cause schizophrenia. KW - transcriptomics KW - Schizophrenia KW - post-mortem JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -