Optimal two-stage design for case-control association analysis incorporating genotyping errors

doi:10.1111/j.1469-1809.2007.00419.x

CSpace > 系统科学研究所

	Optimal two-stage design for case-control association analysis incorporating genotyping errors
	Zuo, Y.1; Zou, G.2,3; Wang, J.2,4 ; Zhao, H.5; Liang, H.3
	2008-05-01
发表期刊	ANNALS OF HUMAN GENETICS
ISSN	0003-4800
卷号	72 页码:375-387
摘要	Two-stage design is a cost effective approach for identifying disease genes in genetic studies and it has received much attention recently. In general, there are two types of two-stage designs that differ on the methods and samples used to measure allele frequencies in the first stage: (1) Individual genotyping is used in the first stage; (2) DNA pooling is used in the first stage. In this paper, we focus on the latter.Zuo et al. (2006) investigated statistical power of such a design, among other things, but the cost of the study was not taken into account. The purpose of this paper is to study the optimal design under the given overall cost. We investigate how to allocate the resources to the two stages. Note that in addition to the measurement errors associated with DNA pooling, genotyping errors are also unavoidable with individual genotyping. Therefore, we discuss the optimal design combining genotyping errors associated with individual genotyping. The joint statistical distributions of test statistics in the first and second stages are derived. For a fixed cost, our results show that the optimal design requires no additional samples in the second stage but only that the samples in the first stage be re-used. When the second stage uses an entirely independent sample, however, the optimal design under a given cost depends on the population allele frequency and allele frequency difference between the case and control groups. For the current genotyping costs, we can roughly allocate 1/3 to 1/2 of the total sample size to the first stage for screening.
关键词	DNA pooling genotyping errors individual genotyping measurement errors power two-stage design
DOI	10.1111/j.1469-1809.2007.00419.x
语种	英语
WOS研究方向	Genetics & Heredity
WOS类目	Genetics & Heredity
WOS记录号	WOS:000254927100010
出版者	BLACKWELL PUBLISHING
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/5341
专题	系统科学研究所
通讯作者	Liang, H.
作者单位	1.Michigan State Univ, Dept Stat & Probabil, E Lansing, MI 48824 USA 2.Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100080, Peoples R China 3.Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY 14642 USA 4.Kyoto Univ, Grad Sch Informat, Dept Appl Math & Phys, Kyoto 6068501, Japan 5.Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA
推荐引用方式 GB/T 7714	Zuo, Y.,Zou, G.,Wang, J.,et al. Optimal two-stage design for case-control association analysis incorporating genotyping errors[J]. ANNALS OF HUMAN GENETICS,2008,72:375-387.
APA	Zuo, Y.,Zou, G.,Wang, J.,Zhao, H.,&Liang, H..(2008).Optimal two-stage design for case-control association analysis incorporating genotyping errors.ANNALS OF HUMAN GENETICS,72,375-387.
MLA	Zuo, Y.,et al."Optimal two-stage design for case-control association analysis incorporating genotyping errors".ANNALS OF HUMAN GENETICS 72(2008):375-387.