Block-based Bayesian epistasis association mapping with application to WTCCC type 1 diabetes data

DOI10.1214/11-AOAS469MaRDI QIDQ652369zbMATH OpenWikidataFDO

Authors Yu Zhang, Jing Zhang, Jun S. Liu

Publication date 14 December 2011

Published in The Annals of Applied Statistics (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1111.5972

zbMATH Keywords

disease association studyLD block

Mathematics Subject Classification ID

Bayesian inference (62F15) Applications of statistics to biology and medical sciences; meta analysis (62P10) Medical applications (general) (92C50) Genetics and epigenetics (92D10)

Abstract: Interactions among multiple genes across the genome may contribute to the risks of many complex human diseases. Whole-genome single nucleotide polymorphisms (SNPs) data collected for many thousands of SNP markers from thousands of individuals under the case--control design promise to shed light on our understanding of such interactions. However, nearby SNPs are highly correlated due to linkage disequilibrium (LD) and the number of possible interactions is too large for exhaustive evaluation. We propose a novel Bayesian method for simultaneously partitioning SNPs into LD-blocks and selecting SNPs within blocks that are associated with the disease, either individually or interactively with other SNPs. When applied to homogeneous population data, the method gives posterior probabilities for LD-block boundaries, which not only result in accurate block partitions of SNPs, but also provide measures of partition uncertainty. When applied to case--control data for association mapping, the method implicitly filters out SNP associations created merely by LD with disease loci within the same blocks. Simulation study showed that this approach is more powerful in detecting multi-locus associations than other methods we tested, including one of ours. When applied to the WTCCC type 1 diabetes data, the method identified many previously known T1D associated genes, including PTPN22, CTLA4, MHC, and IL2RA.

Recommendations

• Bayesian epistasis association mapping via SNP imputation
• Bayesian analysis of case control polygenic etiology studies with missing data
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Cites work

• A dynamic programming algorithm for haplotype block partitioning
• Block-based Bayesian epistasis association mapping with application to WTCCC type 1 diabetes data
• Learning Bayesian networks: The combination of knowledge and statistical data
• Model Selection and Estimation in Regression with Grouped Variables
• Monte Carlo strategies in scientific computing
• Regularization and Variable Selection Via the Elastic Net

Cited in

(7)

• Bayesian epistasis association mapping via SNP imputation
• Detecting epistasis via Markov bases
• Efficient regularized isotonic regression with application to gene-gene interaction search
• Sparse block signal detection and identification for shared cross-trait association analysis
• Bayesian analysis of case control polygenic etiology studies with missing data
• Stochastic Search Gene Suggestion: A Bayesian Hierarchical Model for Gene Mapping
• Block-based Bayesian epistasis association mapping with application to WTCCC type 1 diabetes data

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Uses Software

• Haploview

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