Association of the DTNBP1 Locus with Schizophrenia in a U.S. Population

Abstract

Linkage and association studies have recently implicated dystrobrevin-binding protein 1 (DTNBP1) in the etiology of schizophrenia. We analyzed seven previously tested DTNBP1 single-nucleotide polymorphisms (SNPs) in a cohort of 524 individuals with schizophrenia or schizoaffective disorder and 573 control subjects. The minor alleles of three SNPs (P1578, P1763, and P1765) were positively associated with the diagnosis of schizophrenia or schizoaffective disorder in the white subset of the study cohort (258 cases, 467 controls), with P1578 showing the most significant association (odds ratio 1.76, P =.0026). The same three SNPs were also associated in a smaller Hispanic subset (51 cases, 32 controls). No association was observed in the African American subset (215 cases, 74 controls). A stratified analysis of the white and Hispanic subsets showed association with the minor alleles of four SNPs (P1578, P1763, P1320, and P1765). Again, the most significant association was observed for P1578 (P =.0006). Haplotype analysis supported these findings, with a single risk haplotype significantly overrepresented in the white sample (P =.005). Our study provides further evidence for a role of the DTNBP1 gene in the genetic etiology of schizophrenia.

Cognitive deficits in schizophrenia: short‐term and long‐term

“…Such a conception is also consistent with recent genetic findings, which strongly point to a polygenic model in which multiple genes of small effect individually contribute to illness susceptibility via multiple pathophysiological processes (13). For example, recent evidence suggests that a variant in DTNBP1 (dysbindin), which slightly elevates risk for schizophrenia, is also associated with severity of negative symptoms and generalized cognitive deficits (14)(15)(16). At the same time, variants in DISC1 are associated with persecutory delusions and specific deficits in working memory (17,18).…”

Interleukin 3 and schizophrenia: the impact of sex and family history

“…As seen in several other studies of schizophrenia candidate genes, different samples tend to have different risk haplotypes, [38][39][40][41][42][43][44] including flipping of the risk and protective haplotypes of DTNBP1 gene between the ISHDSF 45 and German nuclear families 46 and other samples. 47,48 In this study, the two family samples identified the same risk and protective haplotypes, but in the case-control sample, the risk haplotype in the family samples become protective (underrepresented in the affected individuals).…”

Analysis of TBX1 Variation in Patients with Psychotic and Affective Disorders

“…Alternatively, the lack of TBX1 association in our sample may be a falsenegative result. Of note, associations of two genes, DTNBP1 and COMT, have been shown in the same cohort (71,72). Statistical power is a common concern when considering negative results in genetic association studies of complex disease.…”