Sex-specific transcriptional and proteomic signatures in schizophrenia

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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 .

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
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
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.
3124 Neurology and psychiatry
3111 Biomedicine
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: publishedVersion

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