Two-stage designs in case-control association analysis.

Genetics
Yijun ZuoH Zhao

Abstract

DNA pooling is a cost-effective approach for collecting information on marker allele frequency in genetic studies. It is often suggested as a screening tool to identify a subset of candidate markers from a very large number of markers to be followed up by more accurate and informative individual genotyping. In this article, we investigate several statistical properties and design issues related to this two-stage design, including the selection of the candidate markers for second-stage analysis, statistical power of this design, and the probability that truly disease-associated markers are ranked among the top after second-stage analysis. We have derived analytical results on the proportion of markers to be selected for second-stage analysis. For example, to detect disease-associated markers with an allele frequency difference of 0.05 between the cases and controls through an initial sample of 1000 cases and 1000 controls, our results suggest that when the measurement errors are small (0.005), approximately 3% of the markers should be selected. For the statistical power to identify disease-associated markers, we find that the measurement errors associated with DNA pooling have little effect on its power. This is in contrast to t...Continue Reading

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Citations

Aug 10, 2007·Journal of Human Genetics·Guolian Kang, Yijun Zuo
Aug 31, 2010·Bioinformatics·Anthony Y C KukYaning Yang
Dec 5, 2008·Biostatistics·Jiexun WangGuohua Zou
Feb 16, 2008·Nucleic Acids Research·Stuart MacgregorPeter M Visscher
Oct 6, 2009·Annals of Human Genetics·Siuli MukhopadhyayHongyan Xu
May 18, 2007·Annual Review of Genomics and Human Genetics·Robert C ElstonGang Zheng
Oct 22, 2008·Human Heredity·Yihong Zhao, Shuang Wang
Dec 23, 2011·BMC Medical Genetics·Ramani AnantharamanFook Tim Chew
Mar 23, 2011·Human Genetics·Charleston W K ChiangJoel N Hirschhorn
Nov 16, 2010·Journal of Clinical Epidemiology·Hsiao-Yuan Huang, Wen-Chung Lee
Nov 10, 2009·Journal of Theoretical Biology·Yijun Zuo, Guolian Kang
Jan 22, 2011·Genetic Epidemiology·Joon Sang LeeHongyu Zhao
May 13, 2009·Biometrics·Minjung KwakGang Zheng
Jun 17, 2010·Genetic Epidemiology·Su Yeon KimRasmus Nielsen
May 28, 2019·Journal of the American Statistical Association·Yaowu Liu, Jun Xie
Jul 8, 2010·Statistical Science : a Review Journal of the Institute of Mathematical Statistics·Duncan C ThomasDaniel O Stram

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