MULTISTAGE SAMPLING FOR GENETIC STUDIES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 过去，为了研究孟德尔病，要仔细确定分离家系以进行分离分析，然后收集扩展的多基因家系进行连锁分析。随后将进行关联研究，使用独立的病例对照样本和/或额外的家庭数据。最近，对于复杂的疾病，最初的抽样是进行全基因组的连锁分析，通常使用独立的同胞对或核心家庭，以确定后续关联研究的候选区域，同样使用病例对照样本和/或额外的家庭数据。我们现在有能力使用100,000-500,000个双等位基因标记进行全基因组关联研究。对于这样的研究，我们特别关注有效的两阶段联合抽样设计，它可以在大约一半的基因分型成本下保持近乎最优的统计能力。同样，如果准确汇集DNA样本的成本超过基因分型成本，通过对混合样本进行基因分型来开始相关性研究也可能是一个可行的选择。最后，我们注意到，对用于连锁分析的家庭数据进行抽样并不是一种应该自动停止的做法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.