A multi-marker test based on family data in genome-wide association study.
BACKGROUND
Complex diseases are believed to be the results of many genes and environmental factors. Hence, multi-marker methods that can use the information of markers from different genes are appropriate for mapping complex disease genes. There already have been several multi-marker methods proposed for case-control studies. In this article, we propose a multi-marker test called a Multi-marker Pedigree Disequilibrium Test (MPDT) to analyze family data from genome-wide association studies. If the parental phenotypes are available, we also propose a two-stage test in which a genomic screening test is used to select SNPs, and then the MPDT is used to test the association of the selected SNPs.


RESULTS
We use simulation studies to evaluate the performance of the MPDT and the two-stage approach. The results show that the MPDT constantly outperforms the single marker transmission/disequilibrium test (TDT) 1. Comparing the power of the two-stage approach with that of the one-stage approach, which approach is more powerful depends on the value of the prevalence; when the prevalence is no less than 10%, the two-stage approach may be more powerful than the one-stage approach. Otherwise, the one-stage approach is more powerful.


CONCLUSIONS
The proposed MPDT, is more powerful than the single marker TDT. When the parental phenotypes are available and the prevalence is no less than 10%, the proposed two-stage approach is more powerful than the one-stage approach.
Zhang
Zhaogong
Z
Department of Mathematical Sciences, Michigan Technological University, Houghton, MI 49931, USA. zhaogong@mtu.edu
Zhang
Shuanglin
S
Sha
Qiuying
Q
D000465:Algorithms; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D010375:Pedigree; D010641:Phenotype
D005819:Genetic Markers