Genome-wide association study detected novel susceptibility genes for social cognition impairment in people with schizophrenia

Abstract

Objectives: People with schizophrenia (SCZ) present serious and generalised deficits in social cognition (SC), which affect negatively patients' functioning and treatment outcomes. The genetic background of SC has been investigated in disorders other than SCZ providing weak and sparse results. Thus, our aim was to explore possible genetic correlates of SC dysfunctions in SCZ patients with a genome-wide study (GWAS) approach. Methods: We performed a GWAS meta-analysis of data coming from two cohorts made of 242 and 160 SCZ patients, respectively. SC was assessed with different tools in order to cover its different domains. Results: We found GWAS significant association between the TMEM74 gene and the patients' ability in social inference as assessed by The Awareness of Social Inference Test; this association was confirmed by both SNP-based analysis (lead SNP rs3019332 p-value ¼ 5.24 Â 10 À9 ) and gene-based analysis (p-value ¼ 1.09 Â 10 À7 ). Moreover, suggestive associations of other genes with different dimensions of SC were also found. Conclusions: Our study shows for the first time GWAS significant or suggestive associations of some gene variants with SC domains in people with SCZ. These findings should stimulate further studies to characterise the genetic underpinning of SC dysfunctions in SCZ.

Improving Knowledge on Pathways to Functional Outcome in Schizophrenia: Main Results From the Italian Network for Research on Psychoses

“…Two studies investigated also genetic aspects in this population ( 121 , 122 ). In particular, one study investigated de novo copy number variations (CNVs) in the whole-genomic DNA obtained from 46 family trios of schizophrenia probands.…”

“…The authors reported the presence of de novo CNVs in genes involved in brain and neural development, suggesting that these alterations could contribute to the genetic vulnerability to the disorder ( 122 ). The study by Gennarelli et al ( 121 ) aimed to explore the genetic basis of social cognition, using a genome-wide study approach. The authors found significant associations between the patients' ability in social inference and the TMEM7M4 gene.…”

Unveiling the Associations between EEG Indices and Cognitive Deficits in Schizophrenia-Spectrum Disorders: A Systematic Review

“…Most subjects with schizophrenia experience a broad range of cognitive deficits in different neurocognitive domains, such as working memory, attention/vigilance, verbal/visual learning, reasoning/problem solving and executive functioning [ 3 , 14 , 33 , 34 , 35 , 36 ]. In addition, subjects with schizophrenia often show impairments in social cognition, a cognitive domain defined as a range of abilities guiding the interpretation of other’s emotions or intentions, leading to informed conclusions and behaviours [ 1 , 2 , 4 , 16 , 25 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ].…”