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

DOI10.1214/11-AOAS469zbMATH Open1228.62152arXiv1111.5972WikidataQ34090919 ScholiaQ34090919MaRDI QIDQ652369FDOQ652369

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)

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.

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

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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)

Cites Work

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

Cited In (5)

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

Uses Software

• Haploview

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