Yale University School of Medicine, New Haven, Connecticut, USA.
BMC Genet. 2005 Dec 30;6 Suppl 1(Suppl 1):S31. doi: 10.1186/1471-2156-6-S1-S31.
Complex disease mapping usually involves a combination of linkage and association techniques. Linkage analysis can scan the entire genome in a few hundred tests. Association tests may involve an even greater number of tests. However, association tests can localize the susceptibility genes more accurately. Using a recently developed combined linkage and association strategy, we analyzed a subset of the Collaborative Study on the Genetics of Alcoholism (COGA) data for the Genetic Analysis Workshop 14 (GAW14). In this analysis, we first employed linkage analysis based on frailty models that take into account age of onset information to establish which regions along the chromosome are likely to harbor disease susceptibility genes for alcohol dependence. Second, we used an association analysis by exploiting linkage disequilibrium to narrow down the peak regions. We also compare the methods with mean identity-by-descent tests and transmission/disequilibrium tests that do not use age of onset information.
复杂疾病图谱通常涉及连锁和关联技术的结合。连锁分析可以在几百次测试中扫描整个基因组。关联测试可能涉及更多的测试。然而，关联测试可以更准确地定位易感基因。利用最近开发的连锁和关联联合策略，我们对 14 届遗传分析工作坊（GAW14）协作酒精遗传学研究（COGA）数据的一个子集进行了分析。在这项分析中，我们首先采用基于脆弱性模型的连锁分析，该模型考虑了发病年龄信息，以确定染色体上哪些区域可能含有酒精依赖症的疾病易感基因。其次，我们利用连锁不平衡进行关联分析，以缩小峰区。我们还将这些方法与不使用发病年龄信息的均值同卵双生子检验和传递/不平衡检验进行了比较。
