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

被引:12
作者
Zuo, Y. [1 ]
Zou, G. [2 ,3 ]
Wang, J. [2 ,4 ]
Zhao, H. [5 ]
Liang, H. [3 ]
机构
[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
关键词
DNA pooling; genotyping errors; individual genotyping; measurement errors; power; two-stage design;
D O I
10.1111/j.1469-1809.2007.00419.x
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
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.
引用
收藏
页码:375 / 387
页数:13
相关论文
共 36 条
[21]   Issues in association analysis: Error control in case-control association studies for disease gene discovery [J].
Ott, J .
HUMAN HEREDITY, 2004, 58 (3-4) :171-174
[22]   Allowing for genotyping error in analysis of unmatched case-control studies [J].
Rice, KM ;
Holmans, R .
ANNALS OF HUMAN GENETICS, 2003, 67 :165-174
[23]   The relative power of family-based and case-control designs for linkage disequilibrium studies of complex human diseases - I. DNA pooling [J].
Risch, N ;
Teng, J .
GENOME RESEARCH, 1998, 8 (12) :1273-1288
[24]   The future of genetic studies of complex human diseases [J].
Risch, N ;
Merikangas, K .
SCIENCE, 1996, 273 (5281) :1516-1517
[25]   Searching for genetic determinants in the new millennium [J].
Risch, NJ .
NATURE, 2000, 405 (6788) :847-856
[26]   Optimal two-stage genotyping in population-based association studies [J].
Satagopan, JM ;
Elston, RC .
GENETIC EPIDEMIOLOGY, 2003, 25 (02) :149-157
[27]   Two-stage designs for gene-disease association studies [J].
Satagopan, JM ;
Verbel, DA ;
Venkatraman, ES ;
Offit, KE ;
Begg, CB .
BIOMETRICS, 2002, 58 (01) :163-170
[28]   Two-stage designs for gene-disease association studies with sample size constraints [J].
Satagopan, JM ;
Venkatraman, ES ;
Begg, CB .
BIOMETRICS, 2004, 60 (03) :589-597
[29]   ERROR FILTRATION, INTERFERENCE, AND THE HUMAN LINKAGE MAP [J].
SHIELDS, DC ;
COLLINS, A ;
BUETOW, KH ;
MORTON, NE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (15) :6501-6505
[30]   Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies [J].
Skol, AD ;
Scott, LJ ;
Abecasis, GR ;
Boehnke, M .
NATURE GENETICS, 2006, 38 (02) :209-213