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Hidden Markov Models for Controlling False Discovery Rate in Genome-Wide Association Analysis

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 802)

Abstract

Genome-wide association studies (GWAS) have shown notable success in identifying susceptibility genetic variants of common and complex diseases. To date, the analytical methods of published GWAS have largely been limited to single single nucleotide polymorphism (SNP) or SNP–SNP pair analysis, coupled with multiplicity control using the Bonferroni procedure to control family wise error rate (FWER). However, since SNPs in typical GWAS are in linkage disequilibrium, simple Bonferonni correction is usually over conservative and therefore leads to a loss of efficiency. In addition, controlling FWER may be too stringent for GWAS where the number of SNPs to be tested is enormous. It is more desirable to control the false discovery rate (FDR). We introduce here a hidden Markov model (HMM)-based PLIS testing procedure for GWAS. It captures SNP dependency by an HMM, and based which, provides precise FDR control for identifying susceptibility loci.

Key words

Genome-wide association SNP Hidden Markov model False discovery rate EM algorithm Multiple tests 

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Computer ScienceNew Jersey Institute of TechnologyNewarkUSA

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