The statistical properties of gene-set analysis

Christiaan A. De Leeuw, Benjamin M. Neale, Tom Heskes, Danielle Posthuma

Research output: Contribution to journalArticleAcademicpeer-review

149 Citations (Scopus)


The rapid increase in loci discovered in genome-wide association studies has created a need to understand the biological implications of these results. Gene-set analysis provides a means of gaining such understanding, but the statistical properties of gene-set analysis are not well understood, which compromises our ability to interpret its results. In this Analysis article, we provide an extensive statistical evaluation of the core structure that is inherent to all gene- set analyses and we examine current implementations in available tools. We show which factors affect valid and successful detection of gene sets and which provide a solid foundation for performing and interpreting gene-set analysis.

Original languageEnglish
Article number6
Pages (from-to)353-364
Number of pages12
JournalNature Reviews Genetics
Issue number6
Publication statusPublished - 1 Jun 2016

Cite this