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Association analysis for quantitative traits by data mining: QHPM

Published online by Cambridge University Press:  13 December 2002

P. ONKAMO
Affiliation:
Karolinska Institute, Department of Biosciences at Novum, SE-14157 Huddinge, Sweden Finnish Genome Center, P.O. Box 63, FIN-00014 University of Helsinki, Finland
V. OLLIKAINEN
Affiliation:
Helsinki Institute for Information Technology, Basic Research Unit, Department of Computer Science, P.O. Box 26, FIN-00014 University of Helsinki, Finland
P. SEVON
Affiliation:
Karolinska Institute, Department of Biosciences at Novum, SE-14157 Huddinge, Sweden Department of Computer Science, P.O. Box 26, FIN-00014 University of Helsinki, Finland
H. T. T. TOIVONEN
Affiliation:
Department of Computer Science, P.O. Box 26, FIN-00014 University of Helsinki, Finland
H. MANNILA
Affiliation:
Helsinki Institute for Information Technology, Basic Research Unit, Department of Computer Science, P.O. Box 26, FIN-00014 University of Helsinki, Finland Helsinki University of Technology, Laboratory of Computer and Information Science, P.O. Box 5400, FIN-02015 HUT, Finland
J. KERE
Affiliation:
Karolinska Institute, Department of Biosciences at Novum, SE-14157 Huddinge, Sweden Finnish Genome Center, P.O. Box 63, FIN-00014 University of Helsinki, Finland
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Abstract

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.

Type
Research Article
Copyright
© University College London 2002

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