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

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 schi-zoaffective 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 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 p.0006). Haplotype analysis supported these findings, with a single risk haplotype significantly overrepresented in the white sample (P p.005). Our study provides further evidence for a role of the DTNBP1 gene in the genetic etiology of schizophrenia. Schizophrenia (MIM #181500) is a common, complex disorder affecting ∼1 % of the population worldwide. Its high heritability (∼80%) and elevated sibling recurrenc