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Originally published as Genetics Published Articles Ahead of Print on October 8, 2006.

Genetics, Vol. 174, 1597-1611, November 2006, Copyright © 2006
doi:10.1534/genetics.106.061275

Association Mapping of Complex Trait Loci With Context-Dependent Effects and Unknown Context Variable

Mikko J. Sillanpää*,1 and Madhuchhanda Bhattacharjee{dagger}

* Rolf Nevanlinna Institute, University of Helsinki, FIN-00014 Helsinki, Finland and {dagger} Department of Mathematics and Statistics, Lancaster University, Lancaster, LA1 4YF, United Kingdom

1 Corresponding author: Department of Mathematics and Statistics, Rolf Nevanlinna Institute, University of Helsinki, P.O. Box 68, FIN-00014 Helsinki, Finland. 
E-mail: mjs{at}rolf.helsinki.fi

A novel method for Bayesian analysis of genetic heterogeneity and multilocus association in random population samples is presented. The method is valid for quantitative and binary traits as well as for multiallelic markers. In the method, individuals are stochastically assigned into two etiological groups that can have both their own, and possibly different, subsets of trait-associated (disease-predisposing) loci or alleles. The method is favorable especially in situations when etiological models are stratified by the factors that are unknown or went unmeasured, that is, if genetic heterogeneity is due to, for example, unknown genes x environment or genes x gene interactions. Additionally, a heterogeneity structure for the phenotype does not need to follow the structure of the general population; it can have a distinct selection history. The performance of the method is illustrated with simulated example of genes x environment interaction (quantitative trait with loosely linked markers) and compared to the results of single-group analysis in the presence of missing data. Additionally, example analyses with previously analyzed cystic fibrosis and type 2 diabetes data sets (binary traits with closely linked markers) are presented. The implementation (written in WinBUGS) is freely available for research purposes from http://www.rni.helsinki.fi/~mjs/.


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Genetics 2006 174: NP. [Full Text]