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Global transmission/disequilibrium tests based on haplotype sharing in multiple candidate genes
Author(s) -
Yu Kai,
Gu C. Charles,
Xiong Chengjie,
An Ping,
Province Michael A.
Publication year - 2005
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.20102
Subject(s) - haplotype , biology , genetics , candidate gene , gene , linkage disequilibrium , test statistic , transmission disequilibrium test , genetic association , statistic , multiple comparisons problem , computational biology , type i and type ii errors , statistical hypothesis testing , haplotype estimation , statistics , allele , mathematics , genotype , single nucleotide polymorphism
It is well recognized that multiple genes are likely contributing to the susceptibility of most common complex diseases. Studying one gene at a time might reduce our chance to identify disease susceptibility genes with relatively small effect sizes. Therefore, it is crucial to develop statistical methods that can assess the effect of multiple genes collectively. Motivated by the increasingly available high‐density markers across the whole human genome, we propose a class of TDT‐type methods that can jointly analyze haplotypes from multiple candidate genes (linked or unlinked). Our approach first uses a linear signed rank statistic to compare at an individual gene level the structural similarity among transmitted haplotypes against that among non‐transmitted haplotypes. The results of the ranked comparisons from all considered genes are subsequently combined into global statistics, which can simultaneously test the association of the set of genes with the disease. Using simulation studies, we find that the proposed tests yield correct type I error rates in stratified populations. Compared with the gene‐by‐gene test, the new global tests appear to be more powerful in situations where all candidate genes are associated with the disease. Genet. Epidemiol . 2005. © 2005 Wiley‐Liss, Inc.

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