CrossRef Open Access 2023 3 sitasi

Clustering Schizophrenia Genes by Their Temporal Expression Patterns Aids Functional Interpretation

Dennis van der Meer Weiqiu Cheng Jaroslav Rokicki Sara Fernandez-Cabello Alexey Shadrin +66 lainnya

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Abstrak

Abstract Background Schizophrenia is a highly heritable brain disorder with a typical symptom onset in early adulthood. The 2-hit hypothesis posits that schizophrenia results from differential early neurodevelopment, predisposing an individual, followed by a disruption of later brain maturational processes that trigger the onset of symptoms. Study design We applied hierarchical clustering to transcription levels of 345 genes previously linked to schizophrenia, derived from cortical tissue samples from 56 donors across the lifespan. We subsequently calculated clustered-specific polygenic risk scores for 743 individuals with schizophrenia and 743 sex- and age-matched healthy controls. Study results Clustering revealed a set of 183 genes that was significantly upregulated prenatally and downregulated postnatally and 162 genes that showed the opposite pattern. The prenatally upregulated set of genes was functionally annotated to fundamental cell cycle processes, while the postnatally upregulated set was associated with the immune system and neuronal communication. We found an interaction between the 2 scores; higher prenatal polygenic risk showed a stronger association with schizophrenia diagnosis at higher levels of postnatal polygenic risk. Importantly, this finding was replicated in an independent clinical cohort of 3233 individuals. Conclusions We provide genetics-based evidence that schizophrenia is shaped by disruptions of separable biological processes acting at distinct phases of neurodevelopment. The modeling of genetic risk factors that moderate each other’s effect, informed by the timing of their expression, will aid in a better understanding of the development of schizophrenia.

Penulis (71)

Dennis van der Meer

Weiqiu Cheng

Jaroslav Rokicki

Sara Fernandez-Cabello

Alexey Shadrin

Olav B Smeland

Friederike Ehrhart

Sinan Gülöksüz

Lotta-Katrin Pries

Bochao Lin

Bart P F Rutten

Jim van Os

Michael O’Donovan

Alexander L Richards

Nils Eiel Steen

Srdjan Djurovic

Lars T Westlye

Ole A Andreassen

Tobias Kaufmann

Genetic Risk and Outcome of Psychosis investigators (GROUP)

Eduardo J Aguilar

Berna Akdede

Köksal Alptekin

Vesile Altınyazar

Silvia Amoretti

Sanja Andric-Petrovic

Celso Arango

Manuel Arrojo

Cem Atbaşoğlu

Miguel Bernardo

Tolga Binbay

Julio Bobes

Eylem Şahin Cankurtaran

Angel Carracedo

Burçin Cihan

Philippe Delespaul

Maria Paz García-Portilla

Javier González-Peñas

Sinan Guloksuz

Güvem Gümüş-Akay

Estela Jiménez-López

Semra Ulusoy Kaymak

Gunter Kenis

Bochao D Lin

Gonzalo López

Jurjen J Luykx

Nadja P Maric

Gisela Mezquida

Marina M Mihaljevic

Tijana Mirjanic

Mara Parellada

Katrin Pries

Olga Rivero

Bart P F Rutten

Pilar A Saiz

Meram Can Saka

Julio Sanjuan

José Luis Santos

Haldun Soygür

Alp Üçok

Halis Ulaş

Jim van Os

Berna Yalınçetin

European Network of National Schizophrenia Networks Studying Gene-Environment Interactions Work Package 6 (EU-GEI WP6)

Behrooz Z Alizadeh

Therese van Amelsvoort

Wiepke Cahn

Lieuwe de Haan

Frederike Schirmbeck

Jim van Os

Wim Veling

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APA MLA BibTeX

Meer, D.v.d., Cheng, W., Rokicki, J., Fernandez-Cabello, S., Shadrin, A., Smeland, O.B. et al. (2023). Clustering Schizophrenia Genes by Their Temporal Expression Patterns Aids Functional Interpretation. https://doi.org/10.1093/schbul/sbad140

@article{meer2023, author = {Dennis van der Meer and Weiqiu Cheng and Jaroslav Rokicki and Sara Fernandez-Cabello and Alexey Shadrin and Olav B Smeland and Friederike Ehrhart and Sinan Gülöksüz and Lotta-Katrin Pries and Bochao Lin and Bart P F Rutten and Jim van Os and Michael O’Donovan and Alexander L Richards and Nils Eiel Steen and Srdjan Djurovic and Lars T Westlye and Ole A Andreassen and Tobias Kaufmann and Genetic Risk and Outcome of Psychosis investigators (GROUP) and Eduardo J Aguilar and Berna Akdede and Köksal Alptekin and Vesile Altınyazar and Silvia Amoretti and Sanja Andric-Petrovic and Celso Arango and Manuel Arrojo and Cem Atbaşoğlu and Miguel Bernardo and Tolga Binbay and Julio Bobes and Eylem Şahin Cankurtaran and Angel Carracedo and Burçin Cihan and Philippe Delespaul and Maria Paz García-Portilla and Javier González-Peñas and Sinan Guloksuz and Güvem Gümüş-Akay and Estela Jiménez-López and Semra Ulusoy Kaymak and Gunter Kenis and Bochao D Lin and Gonzalo López and Jurjen J Luykx and Nadja P Maric and Gisela Mezquida and Marina M Mihaljevic and Tijana Mirjanic and Mara Parellada and Katrin Pries and Olga Rivero and Bart P F Rutten and Pilar A Saiz and Meram Can Saka and Julio Sanjuan and José Luis Santos and Haldun Soygür and Alp Üçok and Halis Ulaş and Jim van Os and Berna Yalınçetin and European Network of National Schizophrenia Networks Studying Gene-Environment Interactions Work Package 6 (EU-GEI WP6) and Behrooz Z Alizadeh and Therese van Amelsvoort and Wiepke Cahn and Lieuwe de Haan and Frederike Schirmbeck and Jim van Os and Wim Veling}, title = {Clustering Schizophrenia Genes by Their Temporal Expression Patterns Aids Functional Interpretation}, year = {2023}, journal = {CrossRef}, doi = {10.1093/schbul/sbad140}, url = {https://doi.org/10.1093/schbul/sbad140}, }

Akses Cepat

Lihat di Sumber doi.org/10.1093/schbul/sbad140

Informasi Jurnal

Tahun Terbit: 2023
Bahasa: en
Total Sitasi: 3×
Sumber Database: CrossRef
DOI: 10.1093/schbul/sbad140
Akses: Open Access ✓