مقاله انگلیسی رایگان در مورد ارتباط بین تغییرات در اختلال ژن اسکیزوفرنی 1 و اسکیزوفرنی – الزویر 2018

Schizophrenia is a severe psychiatric disorder. Genetic and functional studies have strongly implicated the disrupted in schizophrenia 1 gene (DISC1) as a candidate susceptibility gene for schizophrenia. Moreover, recent association studies have indicated that several DISC1 single nucleotide polymorphisms (SNPs) are associated with schizophrenia. However, the association is hardly replicate in different ethnic group. Here, we performed a meta-analysis of the association between DISC1 SNPs and schizophrenia in which the samples were divided into subgroups according to ethnicity. Both rs3738401 and rs821616 showed not significantly association with schizophrenia in the Caucasian, Asian, Japanese or Han Chinese populations.

Schizophrenia is a devastating mental illness, with a worldwide prevalence of approximately 1% (Sullivan et al., 2003). It is characterized by emotional impairment, cognitive deficits, and social dysfunction. Evidence from multiple studies indicated that genetic factors play an important role in the etiology of schizophrenia (Faraone et al., 2002). The 414 kb disrupted in schizophrenia 1 gene (DISC1), first identified at the site of a balanced translocation (1;11)(q42.1;q14.3), co-segregates with schizophrenia and other psychiatric disorders in a Scottish pedigree (Millar et al., 2000; Blackwood et al., 2001). Subsequently, the association of several coding or non-coding DISC1 single nucleotide polymorphisms (SNPs) with schizophrenia was independently reported in different ethnic groups (Ekelund et al., 2004; Zhang et al., 2005; Zhang et al., 2006; Chen et al., 2007; Qu et al., 2007; Saetre et al., 2008; Hennah et al., 2009). DISC1 acts as a scaffold protein that interacts with or regulates multiple molecules in neurogenesis, neurodevelopment, neuronal migration, and signaling (Brandon and Sawa, 2011; Porteous et al., 2011; Soares et al., 2011). Mouse models carrying DISC1 mutations show behavioral deficits, and abnormalities in brain morphology, cognitive function, and sociability, which are reminiscent of the findings in schizophrenia (Clapcote et al., 2007; Hikida et al., 2007; Li et al., 2007; Kvajo et al., 2008; Lee et al., 2011; Zhou et al., 2013). Thus, the evidence seems strong for a role of DISC1 in the etiology of schizophrenia. However, genome-wide association studies failed to identify an association between DISC1 and schizophrenia (Brandon and Sawa, 2011; Schizophrenia Working Group of the Psychiatric Genomics, 2014), and this was confirmed by two previous meta-analyses in the same year (Kinoshita et al., 2012; Mathieson et al., 2012). In the present study, we conducted a meta-analysis covering several recent genetic studies focusing on the association of DISC1 variants with schizophrenia (Ratta-Apha et al., 2013; Luo et al., 2015; He et al., 2016; Luo et al., 2016), in which we divided the genetic studies into groups according to ethnicity for subgroup analysis. This meta-analysis revealed no significant association of the DISC1 with schizophrenia.