Format

Send to

Choose Destination
See comment in PubMed Commons below
Bioinformatics. 2012 Jul 1;28(13):1738-44. doi: 10.1093/bioinformatics/bts261. Epub 2012 May 4.

A novel variational Bayes multiple locus Z-statistic for genome-wide association studies with Bayesian model averaging.

Author information

1
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 98109, Seattle, WA 98195, USA. blogsdon@fhcrc.org

Abstract

MOTIVATION:

For many complex traits, including height, the majority of variants identified by genome-wide association studies (GWAS) have small effects, leaving a significant proportion of the heritable variation unexplained. Although many penalized multiple regression methodologies have been proposed to increase the power to detect associations for complex genetic architectures, they generally lack mechanisms for false-positive control and diagnostics for model over-fitting. Our methodology is the first penalized multiple regression approach that explicitly controls Type I error rates and provide model over-fitting diagnostics through a novel normally distributed statistic defined for every marker within the GWAS, based on results from a variational Bayes spike regression algorithm.

RESULTS:

We compare the performance of our method to the lasso and single marker analysis on simulated data and demonstrate that our approach has superior performance in terms of power and Type I error control. In addition, using the Women's Health Initiative (WHI) SNP Health Association Resource (SHARe) GWAS of African-Americans, we show that our method has power to detect additional novel associations with body height. These findings replicate by reaching a stringent cutoff of marginal association in a larger cohort.

AVAILABILITY:

An R-package, including an implementation of our variational Bayes spike regression (vBsr) algorithm, is available at http://kooperberg.fhcrc.org/soft.html.

PMID:
22563072
PMCID:
PMC3381972
DOI:
10.1093/bioinformatics/bts261
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems Icon for PubMed Central Icon for Fred Hutchinson Cancer Research Ctr Arnold Library
    Loading ...
    Support Center