Motivation: The flexibility of a Bayesian framework is promising for GWAS, but current approaches can benefit from more informative prior models. We introduce a novel Bayesian approach to GWAS, called Structured and Non-Local Priors (SNLPs) GWAS, that improves over existing methods in two important ways. First, we describe a model that allows for a marker's gene-parent membership and other characteristics to influence its probability of association with an outcome. Second, we describe a non-local alternative model for differential minor allele rates at each marker, in which the null and alternative hypotheses have no common support. Results: We employ a non-parametric model that allows for clustering of the genes in tandem with a regression model for marker-level covariates, and demonstrate how incorporating these additional characteristics can improve power. We further demonstrate that our non-local alternative model gives symmetric rates of convergence for the null and alternative hypotheses, whereas commonly used local alternative models have asymptotic rates that favor the alternative hypothesis over the null. We demonstrate the robustness and flexibility of our structured and non-local model for different data generating scenarios and signal-to-noise ratios. We apply our Bayesian GWAS method to single nucleotide polymorphisms data collected from a pool of Alzheimer's disease and cognitively normal patients from the Alzheimer's Database Neuroimaging Initiative.
Bibliographical noteFunding Information:
Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through contributions from: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research funds ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
This work was supported by T32 GM108557: NIGMS T32 Interdisciplinary Biostatistics Training in Genetics and Genomics grant, and by NIH grant 1R01-GM130622.
© 2019 The Author(s) . Published by Oxford University Press. All rights reserved.
Copyright 2020 Elsevier B.V., All rights reserved.
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural