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A thalamo-cortical genetic co-expression network is associated with thalamic functional connectivity linked with familial risk for schizophrenia

Published online by Cambridge University Press:  23 March 2020

R. Passiatore
Affiliation:
University of Bari “Aldo Moro”, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Bari, Italy University of Bari “Aldo Moro”, Department of Educational Sciences, Psychology and Communication Sciences, Bari, Italy
L.A. Antonucci
Affiliation:
University of Bari “Aldo Moro”, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Bari, Italy University of Bari “Aldo Moro”, Department of Educational Sciences, Psychology and Communication Sciences, Bari, Italy
P. Di Carlo
Affiliation:
University of Bari “Aldo Moro”, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Bari, Italy
M. Papalino
Affiliation:
University of Bari “Aldo Moro”, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Bari, Italy
A. Monda
Affiliation:
University of Bari “Aldo Moro”, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Bari, Italy
P. Taurisano
Affiliation:
University of Bari “Aldo Moro”, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Bari, Italy
A. Bertolino
Affiliation:
University of Bari “Aldo Moro”, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Bari, Italy Bari University Hospital, Psychiatry Unit, Bari, Italy
G. Pergola
Affiliation:
University of Bari “Aldo Moro”, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Bari, Italy
G. Blasi
Affiliation:
University of Bari “Aldo Moro”, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Bari, Italy Bari University Hospital, Psychiatry Unit, Bari, Italy

Abstract

Introduction

The genetic architecture of schizophrenia is based on polygenic trajectories. Indeed, genes converge on molecular co-expression pathways, which may be associated with heritable characteristics of patients and their siblings, called intermediate phenotypes, such as prefrontal anomalies and thalamic dysconnectivity during attentional control [2].

Objectives

Here, we investigated in healthy humans association between co-expression of genes with coordinated thalamo-prefrontal (THA-PFC) expression and functional connectivity during attentional control.

Methods

We used Brainspan dataset to characterize a coordinated THA-PFC expression gene list by correlating post-mortem gene expression in both areas (Kendall's Tau>.76, Bonferroni P < .05). Then, we identified a PFC co-expression network1 and tested all gene sets for THA-PFC and PGC loci [3] enrichments (P < .05). SNPs associated with the first principal component of the resulting enriched gene set were combined in a Polygenic Co-Expression Index (PCI) [1]. We conducted Independent Component Analysis (ICA) on attentional control fMRI data (n = 265) and selected Independent Components (ICs) including the thalamus and being highly correlated with an attentional control network2. Multiple regressions were conducted (predictor: PCI) using a thalamic cluster previously associated with familial risk for schizophrenia [2] as ROI (FWE P < .05).

Results

In one of the 8 ICs of interest there was a positive effect of PCI on thalamic connectivity strength in a cluster overlapping with our ROI (Z = 4.3).

Conclusion

Decreased co-expression of genes included in PCI predicts thalamic dysconnectivity during attentional control, suggesting a novel co-regulated molecular pathway potentially implicated in genetic risk for schizophrenia.

Disclosure of interest

The authors have not supplied their declaration of competing interest.

Type
e-Poster Viewing: Schizophrenia and other psychotic disorders
Copyright
Copyright © European Psychiatric Association 2017

References

Pergola, G., et al. Transl Psych 201610.1038/tp.2016.253[In press]Google Scholar
Antonucci, L.A., et al.Sch Res 2016; 173: 232910.1016/j.schres.2016.03.014CrossRefGoogle Scholar
Ripke, S., et al.Nature 2014; 511: 421427Google Scholar
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