Testing for genetic association taking into account phenotypic information of relatives.
We investigated efficient case-control association analysis using family data. The outcome of interest was coronary heart disease. We employed existing and new methods that take into account the correlations among related individuals to obtain the proper type I error rates. The methods considered for autosomal single-nucleotide polymorphisms were: 1) generalized estimating equations-based methods, 2) variance-modified Cochran-Armitage (MCA) trend test incorporating kinship coefficients, and 3) genotypic modified quasi-likelihood score test. Additionally, for X-linked single-nucleotide polymorphisms we proposed a two-degrees-of-freedom test. Performance of these methods was tested using Framingham Heart Study 500 k array data.
Uh
Hae-Won
HW
Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, PO Box 9600, Leiden 2300RC, The Netherlands. h.uh@lumc.nl.
Wijk
Henk Jan van der
HJ
Houwing-Duistermaat
Jeanine J
JJ