Joint linkage and segregation analysis under multiallelic trait inheritance: simplifying interpretations for complex traits.
Identification of the genetic basis of common traits may be hindered by underlying complex genetic architectures that are inadequately captured by existing models, including both multiallelic and multilocus modes of inheritance (MOI). One useful approach for localizing genes underlying continuous complex traits is the joint oligogenic linkage and segregation analysis implemented in the package Loki. The method uses reversible jump Markov chain Monte Carlo to eliminate the need to prespecify the number of quantitative trait loci (QTLs) in the trait model, thus providing posterior distributions for the number of QTLs in a Bayesian framework. The current implementation assumes QTLs are diallelic, and therefore can overestimate the number of linked QTLs in the presence of a multiallelic QTL. To address the possibility of multiple alleles, we extended the QTL model to allow for a variable number of additive alleles at each locus. Application to simulated data shows that, under a diallelic MOI, the multiallelic and diallelic analysis models give similar results. Under a multiallelic MOI, the multiallelic analysis model provides better mixing and improved convergence, and leads to a more accurate estimate of the underlying trait MOI and model parameter values, than does the diallelic model. Application to real data shows the multiallelic model results in fewer estimated linked QTLs and that the predominant QTL model is similar to one of two predominant models estimated from the diallelic analysis. Our results indicate that use of a multiallelic analysis model can lead to better understanding of the genetic architecture underlying complex traits.
Rosenthal
Elisabeth A
EA
Division of Medical Genetics and Department of Biostatistics, University of Washington, Seattle, WA 98195-7720, USA.
Wijsman
Ellen M
EM
D000483:Alleles; D001499:Bayes Theorem; D003198:Computer Simulation; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008390:Markov Chains; D008957:Models, Genetic; D015233:Models, Statistical; D009010:Monte Carlo Method; D010641:Phenotype; D040641:Quantitative Trait Loci; D012984:Software