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Sex-specific transcriptional and proteomic signatures in schizophrenia

Author

Listed:
  • Jari Tiihonen

    (Karolinska Institutet
    University of Eastern Finland, Niuvanniemi Hospital)

  • Marja Koskuvi

    (University of Eastern Finland
    University of Helsinki)

  • Markus Storvik

    (University of Eastern Finland)

  • Ida Hyötyläinen

    (University of Eastern Finland)

  • Yanyan Gao

    (University of Eastern Finland)

  • Katja A. Puttonen

    (University of Eastern Finland)

  • Raisa Giniatullina

    (University of Eastern Finland)

  • Ekaterina Poguzhelskaya

    (University of Eastern Finland)

  • Ilkka Ojansuu

    (University of Eastern Finland, Niuvanniemi Hospital)

  • Olli Vaurio

    (University of Eastern Finland, Niuvanniemi Hospital)

  • Tyrone D. Cannon

    (Yale University)

  • Jouko Lönnqvist

    (National Institute for Health and Welfare
    University of Helsinki)

  • Sebastian Therman

    (National Institute for Health and Welfare)

  • Jaana Suvisaari

    (National Institute for Health and Welfare)

  • Jaakko Kaprio

    (University of Helsinki
    University of Helsinki)

  • Lesley Cheng

    (La Trobe University)

  • Andrew F. Hill

    (La Trobe University)

  • Markku Lähteenvuo

    (University of Eastern Finland, Niuvanniemi Hospital
    University of Helsinki)

  • Jussi Tohka

    (University of Eastern Finland)

  • Rashid Giniatullin

    (University of Eastern Finland)

  • Šárka Lehtonen

    (University of Eastern Finland
    University of Helsinki)

  • Jari Koistinaho

    (University of Eastern Finland
    University of Helsinki)

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.

Suggested Citation

  • Jari Tiihonen & Marja Koskuvi & Markus Storvik & Ida Hyötyläinen & Yanyan Gao & Katja A. Puttonen & Raisa Giniatullina & Ekaterina Poguzhelskaya & Ilkka Ojansuu & Olli Vaurio & Tyrone D. Cannon & Jouk, 2019. "Sex-specific transcriptional and proteomic signatures in schizophrenia," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11797-3
    DOI: 10.1038/s41467-019-11797-3
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