Bayesian association-based fine mapping in small chromosomal segments

Genetics
M J Sillanpää, Madhuchhanda Bhattacharjee

Abstract

A Bayesian method for fine mapping is presented, which deals with multiallelic markers (with two or more alleles), unknown phase, missing data, multiple causal variants, and both continuous and binary phenotypes. We consider small chromosomal segments spanned by a dense set of closely linked markers and putative genes only at marker points. In the phenotypic model, locus-specific indicator variables are used to control inclusion in or exclusion from marker contributions. To account for covariance between consecutive loci and to control fluctuations in association signals along a candidate region we introduce a joint prior for the indicators that depends on genetic or physical map distances. The potential of the method, including posterior estimation of trait-associated loci, their effects, linkage disequilibrium pattern due to close linkage of loci, and the age of a causal variant (time to most recent common ancestor), is illustrated with the well-known cystic fibrosis and Friedreich ataxia data sets by assuming that haplotypes were not available. In addition, simulation analysis with large genetic distances is shown. Estimation of model parameters is based on Markov chain Monte Carlo (MCMC) sampling and is implemented using Wi...Continue Reading

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Citations

Jul 24, 2008·Heredity·M J Sillanpää, N Noykova
Jun 25, 2008·Annals of Human Genetics·M-Y TsaiS-H Wen
Sep 14, 2012·Annals of Human Genetics·Hanni P Kärkkāinen, Mikko J Sillanpää
Aug 7, 2007·PLoS Genetics·Bertrand Servin, Matthew Stephens
Mar 3, 2006·Genetics·Sung KimPaul Marjoram
Oct 10, 2006·Genetics·Mikko J Sillanpää, Madhuchhanda Bhattacharjee
Jan 19, 2008·Genetics·Jianming YuEdward S Buckler
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Jan 10, 2009·TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik·Hiroyoshi IwataTakeshi Hayashi
Jul 25, 2012·TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik·Crispin M Mutshinda, Mikko J Sillanpää
Nov 26, 2009·Briefings in Bioinformatics·Zhiwu ZhangPeter J Bradbury

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