Genetic association studies of copy-number variation: Should assignment of copy number states precede testing?

Patrick Breheny, Prabhakar Chalise, Anthony Batzler, Liewei M Wang, Brooke L. Fridley

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Recently, structural variation in the genome has been implicated in many complex diseases. Using genomewide single nucleotide polymorphism (SNP) arrays, researchers are able to investigate the impact not only of SNP variation, but also of copy-number variants (CNVs) on the phenotype. The most common analytic approach involves estimating, at the level of the individual genome, the underlying number of copies present at each location. Once this is completed, tests are performed to determine the association between copy number state and phenotype. An alternative approach is to carry out association testing first, between phenotype and raw intensities from the SNP array at the level of the individual marker, and then aggregate neighboring test results to identify CNVs associated with the phenotype. Here, we explore the strengths and weaknesses of these two approaches using both simulations and real data from a pharmacogenomic study of the chemotherapeutic agent gemcitabine. Our results indicate that pooled marker-level testing is capable of offering a dramatic increase in power (> 12-fold) over CNV-level testing, particularly for small CNVs. However, CNV-level testing is superior when CNVs are large and rare; understanding these tradeoffs is an important consideration in conducting association studies of structural variation.

Original languageEnglish (US)
Article numbere34262
JournalPLoS One
Volume7
Issue number4
DOIs
StatePublished - Apr 6 2012

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Genetic Association Studies
Polymorphism
Single Nucleotide Polymorphism
Phenotype
Nucleotides
Testing
gemcitabine
single nucleotide polymorphism
phenotype
Genomic Structural Variation
Genes
testing
pharmacogenomics
genome
Research Personnel
Genome
researchers

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Genetic association studies of copy-number variation : Should assignment of copy number states precede testing? / Breheny, Patrick; Chalise, Prabhakar; Batzler, Anthony; Wang, Liewei M; Fridley, Brooke L.

In: PLoS One, Vol. 7, No. 4, e34262, 06.04.2012.

Research output: Contribution to journalArticle

Breheny, Patrick ; Chalise, Prabhakar ; Batzler, Anthony ; Wang, Liewei M ; Fridley, Brooke L. / Genetic association studies of copy-number variation : Should assignment of copy number states precede testing?. In: PLoS One. 2012 ; Vol. 7, No. 4.
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