Dataset Information

Genomewide multiple-loci mapping in experimental crosses by iterative adaptive penalized regression.

ABSTRACT: Genomewide multiple-loci mapping can be viewed as a challenging variable selection problem where the major objective is to select genetic markers related to a trait of interest. It is challenging because the number of genetic markers is large (often much larger than the sample size) and there is often strong linkage or linkage disequilibrium between markers. In this article, we developed two methods for genomewide multiple loci mapping: the Bayesian adaptive Lasso and the iterative adaptive Lasso. Compared with eight existing methods, the proposed methods have improved variable selection performance in both simulation and real data studies. The advantages of our methods come from the assignment of adaptive weights to different genetic makers and the iterative updating of these adaptive weights. The iterative adaptive Lasso is also computationally much more efficient than the commonly used marginal regression and stepwise regression methods. Although our methods are motivated by multiple-loci mapping, they are general enough to be applied to other variable selection problems.

SUBMITTER: Sun W

PROVIDER: S-EPMC2870969 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genomewide multiple-loci mapping in experimental crosses by iterative adaptive penalized regression.

Sun Wei W Ibrahim Joseph G JG Zou Fei F

Genetics 20100215 1

Genomewide multiple-loci mapping can be viewed as a challenging variable selection problem where the major objective is to select genetic markers related to a trait of interest. It is challenging because the number of genetic markers is large (often much larger than the sample size) and there is often strong linkage or linkage disequilibrium between markers. In this article, we developed two methods for genomewide multiple loci mapping: the Bayesian adaptive Lasso and the iterative adaptive Lass ...[more]

PMID: 20157003

Similar Datasets

Project description:Penalized Multiple Regression (PMR) can be used to discover novel disease associations in GWAS datasets. In practice, proposed PMR methods have not been able to identify well-supported associations in GWAS that are undetectable by standard association tests and thus these methods are not widely applied. Here, we present a combined algorithmic and heuristic framework for PUMA (Penalized Unified Multiple-locus Association) analysis that solves the problems of previously proposed methods including computational speed, poor performance on genome-scale simulated data, and identification of too many associations for real data to be biologically plausible. The framework includes a new minorize-maximization (MM) algorithm for generalized linear models (GLM) combined with heuristic model selection and testing methods for identification of robust associations. The PUMA framework implements the penalized maximum likelihood penalties previously proposed for GWAS analysis (i.e. Lasso, Adaptive Lasso, NEG, MCP), as well as a penalty that has not been previously applied to GWAS (i.e. LOG). Using simulations that closely mirror real GWAS data, we show that our framework has high performance and reliably increases power to detect weak associations, while existing PMR methods can perform worse than single marker testing in overall performance. To demonstrate the empirical value of PUMA, we analyzed GWAS data for type 1 diabetes, Crohns's disease, and rheumatoid arthritis, three autoimmune diseases from the original Wellcome Trust Case Control Consortium. Our analysis replicates known associations for these diseases and we discover novel etiologically relevant susceptibility loci that are invisible to standard single marker tests, including six novel associations implicating genes involved in pancreatic function, insulin pathways and immune-cell function in type 1 diabetes; three novel associations implicating genes in pro- and anti-inflammatory pathways in Crohn's disease; and one novel association implicating a gene involved in apoptosis pathways in rheumatoid arthritis. We provide software for applying our PUMA analysis framework.

Dataset Information

Genomewide multiple-loci mapping in experimental crosses by iterative adaptive penalized regression.

Publications

Genomewide multiple-loci mapping in experimental crosses by iterative adaptive penalized regression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets