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Genetics
Article . 2011 . Peer-reviewed
License: OUP Standard Publication Reuse
Data sources: Crossref
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Genetics
Article
Data sources: UnpayWall
Genetics
Article . 2011
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Increasing Power of Genome-Wide Association Studies by Collecting Additional Single-Nucleotide Polymorphisms

Authors: Emrah, Kostem; Jose A, Lozano; Eleazar, Eskin;

Increasing Power of Genome-Wide Association Studies by Collecting Additional Single-Nucleotide Polymorphisms

Abstract

Abstract Genome-wide association studies (GWASs) have been effectively identifying the genomic regions associated with a disease trait. In a typical GWAS, an informative subset of the single-nucleotide polymorphisms (SNPs), called tag SNPs, is genotyped in case/control individuals. Once the tag SNP statistics are computed, the genomic regions that are in linkage disequilibrium (LD) with the most significantly associated tag SNPs are believed to contain the causal polymorphisms. However, such LD regions are often large and contain many additional polymorphisms. Following up all the SNPs included in these regions is costly and infeasible for biological validation. In this article we address how to characterize these regions cost effectively with the goal of providing investigators a clear direction for biological validation. We introduce a follow-up study approach for identifying all untyped associated SNPs by selecting additional SNPs, called follow-up SNPs, from the associated regions and genotyping them in the original case/control individuals. We introduce a novel SNP selection method with the goal of maximizing the number of associated SNPs among the chosen follow-up SNPs. We show how the observed statistics of the original tag SNPs and human genetic variation reference data such as the HapMap Project can be utilized to identify the follow-up SNPs. We use simulated and real association studies based on the HapMap data and the Wellcome Trust Case Control Consortium to demonstrate that our method shows superior performance to the correlation- and distance-based traditional follow-up SNP selection approaches. Our method is publicly available at http://genetics.cs.ucla.edu/followupSNPs.

Keywords

Genotype, Models, Genetic, Genome, Human, Reproducibility of Results, Coronary Artery Disease, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Arthritis, Rheumatoid, Diabetes Mellitus, Type 1, Crohn Disease, Diabetes Mellitus, Type 2, Humans, Genetic Predisposition to Disease, Algorithms, Genome-Wide Association Study

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    influence
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
17
Average
Top 10%
Top 10%
hybrid