The role of DTNBP1, NRG1, and AKT1 in the genetics of schizophrenia in Finland

Abstract 

Several putative schizophrenia susceptibility genes have recently been identified. Significant associations between schizophrenia and neuregulin 1 (NRG1) and dysbindin (DTNBP1) were first reported in 2002 and studies in several populations have since independently reported positive associations to these gene regions. Further, both tentative functional and genetic data have implicated the role of AKT1 in the genetic background of this disorder. However, findings have not been consistent in all populations. We investigated the allelic diversity of these three genes NRG1, DTNBP1 and AKT1 in a representative nation-wide study sample of 441 Finnish schizophrenia families consisting of 865 affected individuals, in order to assess their role in one of the largest population-based study samples. DTNBP1 and AKT1 failed to show evidence of association, whereas two SNPs in the 3′ region of the NRG1 gene yielded suggestive evidence of association (p=0.012 and p=0.048) in family-based association analyses. Thus, our study does not indicate that AKT1 or DTNBP1 play a role in the etiology of schizophrenia in the Finnish population. Furthermore, results do not support a major role for NRG1, but we cannot completely exclude a minor role of this gene in the Finnish population.

Abbreviations: AKT1, V-akt murine thymoma viral oncogene homolog 1, CEPH, The Centre d'Etude du Polymorphisme Humain, DISC1, Disrupted in schizophrenia 1, DSM-IV, The Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition, DTNBP, Dystrobrevin binding protein 1, FBAT, Family based association test, MIM, Mendelian inheritance in man, NRG1, Neuregulin 1, LC, Liability class, LD, Linkage disequilibrium, SNP, Single nucleotide polymorphism

Keywords: NRG1, DTNBP1, AKT1, Schizophrenia, Association, Finland