Bayesian Quantitative Trait Loci Mapping for Multiple Traits

Most quantitative trait loci (QTL) mapping experiments typically collect phenotypic data on multiple correlated complex traits. However, there is a lack of a comprehensive genomewide mapping strategy for correlated traits in the literature. We develop Bayesian multiple-QTL mapping methods for correlated continuous traits using two multivariate models: one that assumes the same genetic model for all traits, the traditional multivariate model, and the other known as the seemingly unrelated regression (SUR) model that allows different genetic models for different traits. We develop computationally efficient Markov chain Monte Carlo (MCMC) algorithms for performing joint analysis. We conduct extensive simulation studies to assess the performance of the proposed methods and to compare with the conventional single-trait model. Our methods have been implemented in the freely available package R/qtlbim (http://www.qtlbim.org), which greatly facilitates the general usage of the Bayesian methodology for unraveling the genetic architecture of complex traits.

[1]  Alan J. Miller.  Sélection of subsets of regression variables , 1984 .

[2]  E. Lander,et al.  Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. , 1989, Genetics.

[3]  Z B Zeng,et al.  Multiple trait analysis of genetic mapping for quantitative trait loci. , 1995, Genetics.

[4]  D. Madigan,et al.  Bayesian Model Averaging for Linear Regression Models , 1997 .

[5]  B. Mangin,et al.  PLEIOTROPIC QTL ANALYSIS , 1998 .

[6]  David R. Anderson,et al.  Model Selection and Multimodel Inference , 2003 .

[7]  P. van Eerdewegh,et al.  Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. I. Likelihood formulation and simulation results. , 1999, American journal of human genetics.

[8]  A. Galecki,et al.  Multiple-trait quantitative trait loci analysis using a large mouse sibship. , 1999, Genetics.

[9]  J Blangero,et al.  Joint multipoint linkage analysis of multivariate qualitative and quantitative traits. II. Alcoholism and event-related potentials. , 1999, American journal of human genetics.

[10]  Z B Zeng,et al.  Genotype-environment interaction for quantitative trait loci affecting life span in Drosophila melanogaster. , 2000, Genetics.

[11]  C. Haley,et al.  Multitrait least squares for quantitative trait loci detection. , 2000, Genetics.

[12]  R. Kohn,et al.  Nonparametric seemingly unrelated regression , 2000 .

[13]  G. Churchill,et al.  A statistical framework for quantitative trait mapping. , 2001, Genetics.

[14]  J C Whittaker,et al.  Mapping quantitative trait Loci using generalized estimating equations. , 2001, Genetics.

[15]  William E. Griffiths,et al.  Bayesian Inference in the Seemingly Unrelated Regressions Models , 2001 .

[16]  C. Hackett,et al.  Multi-trait QTL mapping in barley using multivariate regression. , 2001, Genetical research.

[17]  R. Ball,et al.  Bayesian methods for quantitative trait loci mapping based on model selection: approximate analysis using the Bayesian information criterion. , 2001, Genetics.

[18]  David R. Anderson,et al.  Bayesian Methods in Cosmology: Model selection and multi-model inference , 2009 .

[19]  Z. Zeng,et al.  Modeling epistasis of quantitative trait loci using Cockerham's model. , 2002, Genetics.

[20]  Karl W. Broman,et al.  A model selection approach for the identification of quantitative trait loci in experimental crosses , 2002 .

[21]  Nengjun Yi,et al.  Mapping quantitative trait loci with epistatic effects. , 2002, Genetical research.

[22]  M. Sillanpää,et al.  Model choice in gene mapping: what and why. , 2002, Trends in genetics : TIG.

[23]  G. Churchill,et al.  Genetics of colitis susceptibility in IL-10-deficient mice: backcross versus F2 results contrasted by principal component analysis. , 2002, Genomics.

[24]  H. Gilbert,et al.  Comparison of three multitrait methods for QTL detection , 2003, Genetics Selection Evolution.

[25]  William E. Griffiths.  Bayesian Inference in the Seemingly Unrelated Regressions Model , 2003 .

[26]  B. Guldbrandtsen,et al.  Multitrait fine mapping of quantitative trait loci using combined linkage disequilibria and linkage analysis. , 2003, Genetics.

[27]  Hao Wu,et al.  R/qtl: QTL Mapping in Experimental Crosses , 2003, Bioinform..

[28]  Jian Huang,et al.  Genetic linkage analysis of a dichotomous trait incorporating a tightly linked quantitative trait in affected sib pairs. , 2003, American journal of human genetics.

[29]  M. Goddard,et al.  Mapping multiple QTL using linkage disequilibrium and linkage analysis information and multitrait data , 2004, Genetics Selection Evolution.

[30]  Power of three multitrait methods for QTL detection in crossbred populations , 2004, Genetics Selection Evolution.

[31]  Nengjun Yi,et al.  Bayesian model choice and search strategies for mapping interacting quantitative trait Loci. , 2003, Genetics.

[32]  Nengjun Yi,et al.  A Unified Markov Chain Monte Carlo Framework for Mapping Multiple Quantitative Trait Loci , 2004, Genetics.

[33]  Z. Zeng,et al.  Mapping quantitative trait loci with dominant and missing markers in various crosses from two inbred lines , 2004, Genetica.

[34]  Nengjun Yi,et al.  Bayesian Model Selection for Genome-Wide Epistatic Quantitative Trait Loci Analysis , 2005, Genetics.

[35]  Shizhong Xu,et al.  Joint Mapping of Quantitative Trait Loci for Multiple Binary Characters , 2005, Genetics.

[36]  Z. Zeng,et al.  Modeling Quantitative Trait Loci and Interpretation of Models , 2005, Genetics.

[37]  Claudio J. Verzilli,et al.  Bayesian modelling of multivariate quantitative traits using seemingly unrelated regressions , 2005, Genetic epidemiology.

[38]  Shizhong Xu,et al.  Bayesian Shrinkage Estimation of Quantitative Trait Loci Parameters , 2005, Genetics.

[39]  Nengjun Yi,et al.  An Efficient Bayesian Model Selection Approach for Interacting Quantitative Trait Loci Models With Many Effects , 2007, Genetics.

[40]  Shizhong Xu,et al.  Bayesian Shrinkage Analysis of Quantitative Trait Loci for Dynamic Traits , 2007, Genetics.

[41]  H. Deng,et al.  Bayesian mapping of quantitative trait loci for multiple complex traits with the use of variance components. , 2007, American journal of human genetics.

[42]  Hao Wu,et al.  R/qtlbim: QTL with Bayesian Interval Mapping in experimental crosses , 2007, Bioinform..

[43]  R. Byron.  An Efficient Method of Estimating Seemingly Unrelated Regressions and Tests for Aggregation Bias , 2008 .

[44]  N. Yi,et al.  Advances in Bayesian multiple quantitative trait loci mapping in experimental crosses , 2008, Heredity.

[45]  D. Parkinson,et al.  Bayesian Methods in Cosmology: Model selection and multi-model inference , 2009 .

[46]  John K Kruschke,et al.  Bayesian data analysis. , 2010, Wiley interdisciplinary reviews. Cognitive science.