Funke Birgit, Finn Christine T, Plocik Alex M, Lake Stephen, DeRosse Pamela, Kane John M, Kucherlapati Raju, Malhotra Anil K
Harvard Medical School-Partners Center for Genetics and Genomics, Boston, MA 02115, USA.
Am J Hum Genet. 2004 Nov;75(5):891-8. doi: 10.1086/425279. Epub 2004 Sep 10.
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.
连锁分析和关联研究最近表明，肌营养不良蛋白结合蛋白1（DTNBP1）与精神分裂症的病因有关。我们在一个由524名精神分裂症或分裂情感性障碍患者以及573名对照受试者组成的队列中，分析了7个先前已检测过的DTNBP1单核苷酸多态性（SNP）。在研究队列的白人亚组（258例患者，467名对照）中，3个SNP（P1578、P1763和P1765）的次要等位基因与精神分裂症或分裂情感性障碍的诊断呈正相关，其中P1578显示出最显著的相关性（优势比1.76，P = 0.0026）。在一个较小的西班牙裔亚组（51例患者，32名对照）中，同样的3个SNP也存在关联。在非裔美国人亚组（215例患者，74名对照）中未观察到关联。对白人和西班牙裔亚组的分层分析显示，4个SNP（P1578、P1763、P1320和P1765）的次要等位基因存在关联。同样，P1578的相关性最为显著（P = 0.0006）。单倍型分析支持了这些发现，在白人样本中，单一风险单倍型显著过度表达（P = 0.005）。我们的研究为DTNBP1基因在精神分裂症遗传病因学中的作用提供了进一步的证据。
