A genomic lifespan program that reorganises the young adult brain is targeted in schizophrenia

Nathan G Skene, Marcia Roy, Seth G N Grant

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Article numbere17915
Number of pages30
JournaleLIFE
Volume6
Early online date12 Sept 2017
DOIs
Publication statusE-pub ahead of print - 12 Sept 2017

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