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PMID: 15371355 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Bayesian association-based fine mapping in small chromosomal segments.

Genetics ·Vol. 169 ·No. 1 ·2005-01-00 ·Pages 427-39

Sillanpää MJ, Bhattacharjee M

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 WinBUGS. The model specification code is freely available for research purposes from http://www.rni.helsinki.fi/~mjs/.

MeSH Terms
Algorithms Alleles Bayes Theorem Chromosome Mapping Cystic Fibrosis/genetics Friedreich Ataxia/genetics Genetic Linkage Genetic Markers Genotype Haplotypes Humans Models, Genetic Mutation/genetics Phenotype Quantitative Trait, Heritable
Chemicals
Genetic Markers
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sillanpää Mikko J
Rolf Nevanlinna Institute, University of Helsinki, FIN-00014 Helsinki, Finland. [email protected]
Bhattacharjee Madhuchhanda
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
DOI
10.1534/genetics.104.032680
Email
[email protected]
Published
2005-01-00
Epub
2004-00-15
Pages
427-39
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1448870
Subset
IM
External Links
PubMed source DOI: 10.1534/genetics.104.032680 PMC Full Text View journal details
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