Integrative transcriptomics reveals sexually dimorphic microRNA control of the cholinergic/neurokine interface in schizophrenia and bipolar disorder Authors: Sebastian Lobentanzer 1 , Geula Hanin 2 †, Jochen Klein 1 , Hermona Soreq 2 * Affiliations: 1 Department of Pharmacology, College of Pharmacy, Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany. 2 The Edmond and Lily Safra Center for Brain Science and the Life Sciences Institute, The Hebrew University of Jerusalem, Israel 9190401. *hermona.soreq@mail.huji.ac.il †Current address: Department of Genetics, University of Cambridge, Cambridge CB2 3EH, United Kingdom. Summary (135 words): RNA-sequencing analyses are often limited to identifying lowest p-value transcripts, which does not address polygenic phenomena. To overcome this limitation, we developed an integrative approach that combines large scale transcriptomic meta-analysis of patient brain tissues with single-cell sequencing data of CNS neurons, short RNA-sequencing of human male- and female-originated cell lines, and connectomics of transcription factor- and microRNA-interactions with perturbed transcripts. We used this pipeline to analyze cortical transcripts of schizophrenia and bipolar disorder patients. While these pathologies show massive transcriptional parallels, their clinically well-known sexual dimorphisms remain unexplained. Our method explicates the differences between afflicted men and women, and identifies disease- affected pathways of cholinergic transmission and gp130-family neurokine controllers of immune function, interlinked by microRNAs. This approach may open new perspectives for seeking biomarkers and therapeutic targets, also in other transmitter systems and diseases. Manuscript . CC-BY-NC-ND 4.0 International license certified by peer review) is the author/funder. It is made available under a The copyright holder for this preprint (which was not this version posted July 30, 2019. . https://doi.org/10.1101/600932 doi: bioRxiv preprint