Department of Epidemiology and Public Health, Yale University, New Haven, CT 06520, USA.
BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S130. doi: 10.1186/1471-2156-6-S1-S130.
Alcoholism is a complex disease. As with other common diseases, genetic variants underlying alcoholism have been illusive, possibly due to the small effect from each individual susceptible variant, gene x environment and gene x gene interactions and complications in phenotype definition. We conducted association tests, the family-based association tests (FBAT) and the backward haplotype transmission association (BHTA), on the Collaborative Study of the Genetics of Alcoholism (COGA) data provided by Genetic Analysis Workshop (GAW) 14. Efron's local false discovery rate method was applied to control the proportion of false discoveries. For FBAT, we compared the results based on different types of genetic markers (single-nucleotide polymorphisms (SNPs) versus microsatellites) and different phenotype definitions (clinical diagnoses versus electrophysiological phenotypes). Significant association results were found only between SNPs and clinical diagnoses. In contrast, significant results were found only between microsatellites and electrophysiological phenotypes. In addition, we obtained the association results for SNPs and microsatellites using COGA diagnosis as phenotype based on BHTA. In this case, the results for SNPs and microsatellites are more consistent. Compared to FBAT, more significant markers are detected with BHTA.
酗酒是一种复杂的疾病。与其他常见疾病一样，导致酗酒的遗传变异一直难以捉摸，这可能是因为每个易感变异、基因 x 环境和基因 x 基因相互作用以及表型定义中的并发症的影响都很小。我们对遗传分析研讨会 (GAW) 14 提供的协作性酗酒遗传学研究 (COGA) 数据进行了关联测试，包括基于家系的关联测试 (FBAT) 和反向单倍型传递关联 (BHTA)。Efron 的局部错误发现率方法用于控制错误发现的比例。对于 FBAT，我们比较了基于不同类型遗传标记 (单核苷酸多态性 (SNP) 与微卫星) 和不同表型定义 (临床诊断与电生理表型) 的结果。仅在 SNP 与临床诊断之间发现了显著的关联结果。相比之下，仅在微卫星与电生理表型之间发现了显著的关联结果。此外，我们还使用 BHTA 基于 COGA 诊断作为表型获得了 SNP 和微卫星的关联结果。在这种情况下，SNP 和微卫星的结果更为一致。与 FBAT 相比，BHTA 检测到了更多显著的标记。
