Incorporating prior knowledge to increase the power of genome-wide association studies

Ashley Petersen, Justin Spratt, Nathan L. Tintle

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Scopus citations


Typical methods of analyzing genome-wide single nucleotide variant (SNV) data in cases and controls involve testing each variant's genotypes separately for phenotype association, and then using a substantial multiple-testing penalty to minimize the rate of false positives. This approach, however, can result in low power for modestly associated SNVs. Furthermore, simply looking at the most associated SNVs may not directly yield biological insights about disease etiology. SNVset methods attempt to address both limitations of the traditional approach by testing biologically meaningful sets of SNVs (e.g., genes or pathways). The number of tests run in a SNVset analysis is typically much lower (hundreds or thousands instead of millions) than in a traditional analysis, so the false-positive rate is lower. Additionally, by testing SNVsets that are biologically meaningful finding a significant set may more quickly yield insights into disease etiology. In this chapter we summarize the short history of SNVset testing and provide an overview of the many recently proposed methods. Furthermore, we provide detailed step-by-step instructions on how to perform a SNVset analysis, including a substantial number of practical tips and questions that researchers should consider before undertaking a SNVset analysis. Lastly, we describe a companion R package (snvset) that implements recently proposed SNVset methods. While SNVset testing is a new approach, with many new methods still being developed and many open questions, the promise of the approach is worth serious consideration when considering analytic methods for GWAS.

Original languageEnglish (US)
Title of host publicationGenome-Wide Association Studies and Genomic Prediction
PublisherHumana Press Inc.
Number of pages23
ISBN (Print)9781627034463
StatePublished - 2013

Publication series

NameMethods in Molecular Biology
ISSN (Print)1064-3745


  • GWAS
  • Gene set
  • Pathway
  • SNP-set
  • SNVset


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