Association analysis for quantitative traits by data mining: QHPM.
Previously, we have presented a data mining-based algorithmic approach to genetic association analysis, Haplotype Pattern Mining. We have now extended the approach with the possibility of analysing quantitative traits and utilising covariates. This is accomplished by using a linear model for measuring association. We present results with the extended version, QHPM, with simulated quantitative trait data. One data set was simulated with the population simulator package Populus, and another was obtained from GAW12. In the former, there were 2-3 underlying susceptibility genes for a trait, each with several ancestral disease mutations, and 1 or 2 environmental components. We show that QHPM is capable of finding the susceptibility loci, even when there is strong allelic heterogeneity and environmental effects in the disease models. The power of finding quantitative trait loci is dependent on the ascertainment scheme of the data: collecting the study subjects from both ends of the quantitative trait distribution is more effective than using unselected individuals or individuals ascertained based on disease status, but QHPM has good power to localize the genes even with unselected individuals. Comparison with quantitative trait TDT (QTDT) showed that QHPM has better localization accuracy when the gene effect is weak.
Onkamo
P
P
Karolinska Institute, Department of Biosciences at Novum, SE-14157 Huddinge, Sweden. paivi.onkamo@biosci.ki.se
Ollikainen
V
V
Sevon
P
P
Toivonen
H T T
HT
Mannila
H
H
Kere
J
J
D002874:Chromosome Mapping / Q000706:statistics & numerical data*; D004777:Environment; D030342:Genetic Diseases, Inborn / Q000235:genetics; D005819:Genetic Markers; D005828:Genetics, Population; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D008432:Mathematical Computing; D008957:Models, Genetic; D015999:Multivariate Analysis; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D011336:Probability; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D018401:Sample Size
D005819:Genetic Markers