Haplotype association analysis of human disease traits using genotype data of unrelated individuals.
Haplotype inference has become an important part of human genetic data analysis due to its functional and statistical advantages over the single-locus approach in linkage disequilibrium mapping. Different statistical methods have been proposed for detecting haplotype - disease associations using unphased multi-locus genotype data, ranging from the early approach by the simple gene-counting method to the recent work using the generalized linear model. However, these methods are either confined to case - control design or unable to yield unbiased point and interval estimates of haplotype effects. Based on the popular logistic regression model, we present a new approach for haplotype association analysis of human disease traits. Using haplotype-based parameterization, our model infers the effects of specific haplotypes (point estimation) and constructs confidence interval for the risks of haplotypes (interval estimation). Based on the estimated parameters, the model calculates haplotype frequency conditional on the trait value for both discrete and continuous traits. Moreover, our model provides an overall significance level for the association between the disease trait and a group or all of the haplotypes. Featured by the direct maximization in haplotype estimation, our method also facilitates a computer simulation approach for correcting the significance level of individual haplotype to adjust for multiple testing. We show, by applying the model to an empirical data set, that our method based on the well-known logistic regression model is a useful tool for haplotype association analysis of human disease traits.
Tan
Qihua
Q
Department of Clinical Biochemistry and Genetics (KKA), Odense University Hospital, Denmark. qihua.tan@ouh.fyns-amt.dk
Christiansen
Lene
L
Christensen
Kaare
K
Bathum
Lise
L
Li
Shuxia
S
Zhao
Jing Hua
JH
Kruse
Torben A
TA
D003198:Computer Simulation; D005260:Female; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008957:Models, Genetic; D015233:Models, Statistical; D012044:Regression Analysis; D012306:Risk; D012737:Sex Factors