Association study of the dystrobrevin-binding gene with schizophrenia in Australian and Indian samples
Association study of the dystrobrevin-binding gene with schizophrenia in Australian and Indian samples
复制标题
DOI：
10.1375/twin.9.4.531
复制
发表时间：
2006-08-01
影响因子：
0.9
通讯作者：
Nyholt, Dale R.
中科院分区：
文献类型：
--
作者：
Holliday, Elizabeth G.;Handoko, Herlina Y.;Nyholt, Dale R.
许多研究报道了短肌营养不良蛋白结合蛋白1（dysbindin）基因（DTNBP 1）变异与精神分裂症之间的关联。然而，结果的模式是复杂的，到目前为止，没有特定的风险标志物或单倍型一直被确定。在这些研究中测试的单核苷酸多态性（SNP）的数量范围从5到20。我们试图复制以前的研究结果，通过测试16个SNP的样本中的41个澳大利亚家系，194个澳大利亚病例和180个对照，以及197个印度家系。在任何样本中均未观察到具有全球意义的相关性证据，尽管功效计算表明有足够的功效复制先前的几项发现。对我们结果的可能解释包括背景连锁不平衡和/或风险等位基因效应大小的样本差异，不同单倍型上存在多个风险等位基因，或多个单倍型上存在单个风险等位基因。一些先前的关联也可能代表假阳性。检查高加索人HapMap第二阶段基因型数据跨越DTNBP 1区域表明，需要40个以上的SNPs满意地评估所有非冗余的变化DTNBP 1及其潜在的监管区域与精神分裂症的关联。需要在多个样本中进行更全面的研究，以确定特定的DTNBP 1变体是否作为精神分裂症的风险因素。
Numerous studies have reported association between variants in the dystrobrevin binding protein 1 (dysbindin) gene (DTNBP1) and schizophrenia. However, the pattern of results is complex and to date, no specific risk marker or haplotype has been consistently identified. The number of single nucleotide polymorphisms (SNPs) tested in these studies has ranged from 5 to 20. We attempted to replicate previous findings by testing 16 SNPs in samples of 41 Australian pedigrees, 194 Australian cases and 180 controls, and 197 Indian pedigrees. No globally significant evidence for association was observed in any sample, despite power calculations indicating sufficient power to replicate several previous findings. Possible explanations for our results include sample differences in background linkage disequilibrium and/or risk allele effect size, the presence of multiple risk alleles upon different haplotypes, or the presence of a single risk allele upon multiple haplotypes. Some previous associations may also represent false positives. Examination of Caucasian HapMap phase II genotype data spanning the DTNBP1 region indicates upwards of 40 SNPs are required to satisfactorily assess all nonredundant variation within DTNBP1 and its potential regulatory regions for association with schizophrenia. More comprehensive studies in multiple samples will be required to determine whether specific DTNBP1 variants function as risk factors for schizophrenia.