QIMR Berghofer

Multi-tissue transcriptome analyses identify genetic mechanisms underlying neuropsychiatric traits.


. We provide comprehensive analyses using transcriptome data from an unprecedented collection of tissues to gain pathophysiological insights into the role of the brain, neuroendocrine factors (adrenal gland) and gastrointestinal systems (colon) in psychiatric disorders. In each tissue, we perform PrediXcan analysis and identify trait-associated genes for schizophrenia (n associations?=?499; n unique genes?=?275), bipolar disorder (n associations?=?17; n unique genes?=?13), attention deficit hyperactivity disorder (n associations?=?19; n unique genes?=?12) and broad depression (n associations?=?41; n unique genes?=?31). Importantly, both PrediXcan and summary-data-based Mendelian randomization/heterogeneity in dependent instruments analyses suggest potentially causal genes in non-brain tissues, showing the utility of these tissues for mapping psychiatric disease genetic predisposition. Our analyses further highlight the importance of joint tissue approaches as 76% of the genes were detected only in difficult-to-acquire tissues.

Authors Gamazon, Eric R; Zwinderman, Aeilko H; Cox, Nancy J; Denys, Damiaan; Derks, Eske M
Pages 933-940
Volume 51
Date 1/05/2019
Grant ID R01 MH113362
Funding Body NIMH NIH HHS
URL http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1038/s41588-019-0409-8