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001019094 1001_ $$0P:(DE-HGF)0$$aPergola, Giulio$$b0$$eCorresponding author
001019094 245__ $$aA miR-137-related biological pathway of risk for Schizophrenia is associated with human brain emotion processing
001019094 260__ $$aAmsterdam [u.a.]$$bElsevier Inc.$$c2024
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001019094 520__ $$aBackgroundMiR-137 is a microRNA involved in brain development, regulating neurogenesis and neuronal maturation. Genome-Wide Association Studies implicate miR-137 in schizophrenia risk but do not explain its involvement in brain function and underlying biology. Polygenic risk for schizophrenia mediated by miR-137 targets is associated with working memory, although other evidence points to emotion processing. We characterized the functional brain correlates of miR-137 target genes associated with schizophrenia while disentangling previously reported associations of miR-137 targets with working memory and emotion processing.MethodsUsing RNA-sequencing data from postmortem prefrontal cortex (N=522), we identified a co-expression gene set enriched for miR-137 targets and schizophrenia risk genes. We validated the relationship of this set to miR-137 in-vitro by manipulating miR-137 expression in neuroblastoma cells. We translated this gene set into polygenic scores of co-expression prediction and associated them with fMRI activation in healthy volunteers (N1=214; N2=136; N3=2,075; N4=1,800) and with short-term treatment response in patients with schizophrenia (N=427).ResultsIn 4,652 human subjects, we found that (i) schizophrenia risk genes are co-expressed in a biologically validated set enriched for miR-137 targets, (ii) increased expression of miR-137 target risk genes is mediated by low prefrontal miR-137 expression, (iii) alleles predicting greater gene-set co-expression are associated with greater prefrontal activation during emotion processing in three independent healthy cohorts (N1-2-3), in interaction with age (N4), (iv) these alleles predict less improvement in negative symptoms following antipsychotic treatment in patients with schizophrenia.
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001019094 7001_ $$0P:(DE-HGF)0$$aRampino, Antonio$$b1
001019094 7001_ $$0P:(DE-HGF)0$$aSportelli, Leonardo$$b2
001019094 7001_ $$0P:(DE-HGF)0$$aBorcuk, Christopher James$$b3
001019094 7001_ $$0P:(DE-Juel1)195972$$aPassiatore, Roberta$$b4
001019094 7001_ $$0P:(DE-HGF)0$$aDi Carlo, Pasquale$$b5
001019094 7001_ $$0P:(DE-HGF)0$$aMarakhovskaia, Aleksandra$$b6
001019094 7001_ $$0P:(DE-HGF)0$$aFazio, Leonardo$$b7
001019094 7001_ $$0P:(DE-HGF)0$$aAmoroso, Nicola$$b8
001019094 7001_ $$0P:(DE-HGF)0$$aCastro, Mariana Nair$$b9
001019094 7001_ $$0P:(DE-HGF)0$$aDomenici, Enrico$$b10
001019094 7001_ $$0P:(DE-HGF)0$$aGennarelli, Massimo$$b11
001019094 7001_ $$0P:(DE-HGF)0$$aKhlghatyan, Jivan$$b12
001019094 7001_ $$0P:(DE-HGF)0$$aKikidis, Gianluca Christos$$b13
001019094 7001_ $$0P:(DE-HGF)0$$aLella, Annalisa$$b14
001019094 7001_ $$0P:(DE-HGF)0$$aMagri, Chiara$$b15
001019094 7001_ $$0P:(DE-HGF)0$$aMonaco, Alfonso$$b16
001019094 7001_ $$0P:(DE-HGF)0$$aPapalino, Marco$$b17
001019094 7001_ $$0P:(DE-HGF)0$$aParihar, Madhur$$b18
001019094 7001_ $$0P:(DE-HGF)0$$aPopolizio, Teresa$$b19
001019094 7001_ $$0P:(DE-HGF)0$$aQuarto, Tiziana$$b20
001019094 7001_ $$0P:(DE-HGF)0$$aRomano, Raffaella$$b21
001019094 7001_ $$0P:(DE-HGF)0$$aTorretta, Silvia$$b22
001019094 7001_ $$0P:(DE-HGF)0$$aValsecchi, Paolo$$b23
001019094 7001_ $$0P:(DE-HGF)0$$aZunuer, Hediche$$b24
001019094 7001_ $$0P:(DE-HGF)0$$aBlasi, Giuseppe$$b25
001019094 7001_ $$0P:(DE-Juel1)177727$$aDukart, Jürgen$$b26
001019094 7001_ $$0P:(DE-HGF)0$$aBeaulieu, Jean Martin$$b27
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001019094 9101_ $$0I:(DE-HGF)0$$6P:(DE-HGF)0$$aGiulio Pergola, PhD, Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari Aldo Moro$$b0
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