Date of Original Version

6-15-2010

Type

Article

PubMed ID

20529908

Rights Management

© The Author(s) 2010. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract or Description

MOTIVATION: Population heterogeneity through admixing of different founder populations can produce spurious associations in genome-wide association studies that are linked to the population structure rather than the phenotype. Since samples from the same population generally co-evolve, different populations may or may not share the same genetic underpinnings for the seemingly common phenotype. Our goal is to develop a unified framework for detecting causal genetic markers through a joint association analysis of multiple populations.

RESULTS: Based on a multi-task regression principle, we present a multi-population group lasso algorithm using L(1)/L(2)-regularized regression for joint association analysis of multiple populations that are stratified either via population survey or computational estimation. Our algorithm combines information from genetic markers across populations, to identify causal markers. It also implicitly accounts for correlations between the genetic markers, thus enabling better control over false positive rates. Joint analysis across populations enables the detection of weak associations common to all populations with greater power than in a separate analysis of each population. At the same time, the regression-based framework allows causal alleles that are unique to a subset of the populations to be correctly identified. We demonstrate the effectiveness of our method on HapMap-simulated and lactase persistence datasets, where we significantly outperform state of the art methods, with greater power for detecting weak associations and reduced spurious associations.

AVAILABILITY: Software will be available at http://www.sailing.cs.cmu.edu/.

DOI

10.1093/bioinformatics/btq191

Creative Commons


This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License

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Published In

Bioinformatics, 26, 12, 208-216.