Structured Genome-Wide Association Studies with Bayesian Hierarchical Variable Selection

Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation

Zhaohua Lu^3¹  Fei Zou^5²  Hongtu Zhu^2³  Yize Zhao^1⁴  Rebecca C. Knickmeyer^4⁵ 

[1] Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105^3;Department of Biostatistics, University of Florida, Gainesville, Florida 32611^5;Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina 27599^2;Department of Healthcare Policy and Research, Cornell University Weill Cornell, New York, New York 10065^1;Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan 48824^4

关键词: imaging genetics;    genome-wide association studies;    SNP-set;    Bayesian variable selection;    Markov chain Monte Carlo;   

DOI  :  10.1534/genetics.119.301906

学科分类：医学（综合）

来源: Genetics Society of America

【 摘 要 】

It becomes increasingly important in using genome-wide association studies (GWAS) to select important genetic information associated with qualitative or quantitative traits. Currently, the discovery of biological association among SNPs motivates various strategies to construct SNP-sets along the genome and to incorporate such set information into selection procedure for a higher selection power, while facilitating more biologically meaningful results. The aim of this paper is to propose a novel Bayesian framework for hierarchical variable selection at both SNP-set (group) level and SNP (within group) level. We overcome a key limitation of existing posterior updating scheme in most Bayesian variable selection methods by proposing a novel sampling scheme to explicitly accommodate the ultrahigh-dimensionality of genetic data. Specifically, by constructing an auxiliary variable selection model under SNP-set level, the new procedure utilizes the posterior samples of the auxiliary model to subsequently guide the posterior inference for the targeted hierarchical selection model. We apply the proposed method to a variety of simulation studies and show that our method is computationally efficient and achieves substantially better performance than competing approaches in both SNP-set and SNP selection. Applying the method to the Alzheimers Disease Neuroimaging Initiative (ADNI) data, we identify biologically meaningful genetic factors under several neuroimaging volumetric phenotypes. Our method is general and readily to be applied to a wide range of biomedical studies.

【 授权许可】

CC BY