Tiihonen , J , Koskuvi , M , Storvik , M , Hyotylainen , I , Gao , Y , Puttonen , K A , Giniatullina , R , Poguzhelskaya , E , Ojansuu , I , Vaurio , O , Cannon , T D , Lonnqvist , J , Therman , S , Suvisaari , J , Kaprio , J , Cheng , L , Hill , A F , Lahteenvuo , M , Tohka , J , Giniatullin , R , Lehtonen , S & Koistinaho , J 2019 , ' Sex-specific transcriptional and proteomic signatures in schizophrenia ' , Nature Communications , vol. 10 , 3933 . https://doi.org/10.1038/s41467-019-11797-3
Title: | Sex-specific transcriptional and proteomic signatures in schizophrenia |
Author: | Tiihonen, Jari; Koskuvi, Marja; Storvik, Markus; Hyotylainen, Ida; Gao, Yanyan; Puttonen, Katja A.; Giniatullina, Raisa; Poguzhelskaya, Ekaterina; Ojansuu, Ilkka; Vaurio, Olli; Cannon, Tyrone D.; Lonnqvist, Jouko; Therman, Sebastian; Suvisaari, Jaana; Kaprio, Jaakko; Cheng, Lesley; Hill, Andrew F.; Lahteenvuo, Markku; Tohka, Jussi; Giniatullin, Rashid; Lehtonen, Sarka; Koistinaho, Jari |
Contributor organization: | Neuroscience Center HUS Psychiatry Clinicum Department of Psychiatry Helsinki University Hospital Area Institute for Molecular Medicine Finland Department of Public Health Jaakko Kaprio / Principal Investigator Genetic Epidemiology |
Date: | 2019-09-02 |
Language: | eng |
Number of pages: | 11 |
Belongs to series: | Nature Communications |
ISSN: | 2041-1723 |
DOI: | https://doi.org/10.1038/s41467-019-11797-3 |
URI: | http://hdl.handle.net/10138/305436 |
Abstract: | It has remained unclear why schizophrenia typically manifests after adolescence and which neurobiological mechanisms are underlying the cascade leading to the actual onset of the illness. Here we show that the use of induced pluripotent stem cell-derived neurons of monozygotic twins from pairs discordant for schizophrenia enhances disease-specific signal by minimizing genetic heterogeneity. In proteomic and pathway analyses, clinical illness is associated especially with altered glycosaminoglycan, GABAergic synapse, sialylation, and purine metabolism pathways. Although only 12% of all 19,462 genes are expressed differentially between healthy males and females, up to 61% of the illness-related genes are sex specific. These results on sex-specific genes are replicated in another dataset. This implies that the pathophysiology differs between males and females, and may explain why symptoms appear after adolescence when the expression of many sex-specific genes change, and suggests the need for sex-specific treatments. |
Subject: |
ANTIPSYCHOTIC TREATMENT
ASSOCIATION METABOLISM EXPRESSION GENES 3124 Neurology and psychiatry 3111 Biomedicine |
Peer reviewed: | Yes |
Rights: | unspecified |
Usage restriction: | openAccess |
Self-archived version: | publishedVersion |
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