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

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. 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. We found GWAS significant association between the <i>TMEM74</i> 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 <i>p</i>-value = 5.24 × 10⁻⁹) and gene-based analysis (<i>p</i>-value = 1.09 × 10⁻⁷). Moreover, suggestive associations of other genes with different dimensions of SC were also found. 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.

精神分裂症（schizophrenia, SCZ）患者存在广泛且严重的社会认知（social cognition, SC）缺陷，该缺陷会对患者的社会功能与治疗结局产生不利影响。既往针对精神分裂症以外的疾病开展的社会认知遗传背景研究，所得结果均较为薄弱且零散。因此，本研究拟通过全基因组关联研究（genome-wide association study, GWAS）方法，探索精神分裂症患者社会认知功能异常的潜在遗传关联因素。本研究对来自两个队列的数据集开展全基因组关联研究荟萃分析，两个队列分别纳入242名和160名精神分裂症患者。为全面覆盖社会认知的不同维度，研究采用多种工具对受试者的社会认知水平进行评估。研究发现，<i>TMEM74</i>基因与通过社会推理意识测验评估的患者社会推理能力存在全基因组关联研究显著性关联；该关联经基于单核苷酸多态性（single nucleotide polymorphism, SNP）的分析（核心SNP rs3019332，p值=5.24 × 10⁻⁹）以及基于基因的分析（p值=1.09 × 10⁻⁷）均得到验证。此外，本研究还发现了其他基因与社会认知不同维度存在提示性关联。本研究首次在精神分裂症患者群体中，证实部分基因变异与社会认知维度之间存在全基因组关联研究显著性或提示性关联。上述发现将为后续阐明精神分裂症患者社会认知功能异常的遗传基础提供重要研究方向。