Inclusion of biological knowledge in a Bayesian shrinkage model for joint estimation of SNP effects
File(s)Gen Epi 2017.pdf (985.58 KB)
Accepted version
Author(s)
Pereira, M
Thompson, JR
Weichenberger, CX
Thomas, DC
Minelli, C
Type
Journal Article
Abstract
With the aim of improving detection of novel single-nucleotide polymorphisms (SNPs) in genetic association studies, we propose a method of including prior biological information in a Bayesian shrinkage model that jointly estimates SNP effects. We assume that the SNP effects follow a normal distribution centered at zero with variance controlled by a shrinkage hyperparameter. We use biological information to define the amount of shrinkage applied on the SNP effects distribution, so that the effects of SNPs with more biological support are less shrunk toward zero, thus being more likely detected. The performance of the method was tested in a simulation study (1,000 datasets, 500 subjects with ∼200 SNPs in 10 linkage disequilibrium (LD) blocks) using a continuous and a binary outcome. It was further tested in an empirical example on body mass index (continuous) and overweight (binary) in a dataset of 1,829 subjects and 2,614 SNPs from 30 blocks. Biological knowledge was retrieved using the bioinformatics tool Dintor, which queried various databases. The joint Bayesian model with inclusion of prior information outperformed the standard analysis: in the simulation study, the mean ranking of the true LD block was 2.8 for the Bayesian model versus 3.6 for the standard analysis of individual SNPs; in the empirical example, the mean ranking of the six true blocks was 8.5 versus 9.3 in the standard analysis. These results suggest that our method is more powerful than the standard analysis. We expect its performance to improve further as more biological information about SNPs becomes available.
Date Issued
2017-04-10
Date Acceptance
2016-12-26
Citation
GENETIC EPIDEMIOLOGY, 2017, 41 (4), pp.320-331
ISSN
0741-0395
Publisher
WILEY
Start Page
320
End Page
331
Journal / Book Title
GENETIC EPIDEMIOLOGY
Volume
41
Issue
4
Copyright Statement
© 2017 Wiley Periodicals, Inc. This is the accepted version of the following article: Pereira M, Thompson JR, Weichenberger CX, Thomas DC, Minelli C. Inclusion of biological knowledge in a Bayesian shrinkage model for joint estimation of SNP effects. Genet. Epidemiol. 2017;41:320–331. https://doi.org/10.1002/gepi.22038, which has been published in final form at https://dx.doi.org/10.1002/gepi.22038
Sponsor
National Heart & Lung Institute Foundation
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000399712600004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
12PS6-14-17
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
Mathematical & Computational Biology
Bayesian model
genetic association studies
prior knowledge
shrinkage
GENETIC ASSOCIATION
MAXIMUM-LIKELIHOOD
GENOME
PRIORITIZATION
INFORMATION
SELECTION
DATABASE
DISEASE
Bayes Theorem
Body Mass Index
Computer Simulation
Genetic Association Studies
Humans
Linkage Disequilibrium
Models, Genetic
Models, Statistical
Polymorphism, Single Nucleotide
Respiration
Epidemiology
1117 Public Health And Health Services
0604 Genetics
Publication Status
Published