In the past, to study Mendelian diseases, segregating families have been carefully ascertained for segregation analysis, followed by collecting extended multiplex families for linkage analysis. This would then be followed by association studies, using independent case-control samples and/or additional family data. Recently, for complex diseases, the initial sampling has been for a genome-wide linkage analysis, often using independent sib-pairs or nuclear families, to identify candidate regions for follow-up with association studies, again using case-control samples and/or additional family data. We now have the ability to conduct genome-wide association studies using 100,000-500,000 diallelic genetic markers. For such studies we focus especially on efficient two-stage association sampling designs, which can retain nearly optimal statistical power at about half the genotyping cost. Similarly, beginning an association study by genotyping pooled samples may also be a viable option if the cost of accurately pooling DNA samples outweighs genotyping costs. Finally, we note that the sampling of family data for linkage analysis is not a practice that should be automatically discontinued.

中文翻译：

---

遗传研究的多阶段采样。

过去，为了研究孟德尔病，已经仔细确定了隔离家庭以进行隔离分析，然后收集扩展的多重家庭进行连锁分析。然后，将使用独立的病例对照样本和/或其他家族数据进行关联研究。最近，对于复杂的疾病，最初的采样是用于基因组范围的连锁分析，通常使用独立的同胞对或核家族，以鉴定关联研究的候选区域，再次使用病例对照样品和/或其他家庭数据。我们现在有能力使用100,000-500,000个拨号遗传标记进行全基因组关联研究。对于此类研究，我们特别关注高效的两阶段关联抽样设计，它可以保留大约一半基因分型成本的几乎最佳统计能力。同样，如果准确地收集DNA样本的费用超过了基因分型的费用，那么通过对合并样本进行基因分型来开始关联研究也可能是一个可行的选择。最后，我们注意到对家庭数据进行链接分析的采样不是一种应自动终止的做法。