Strategies for Imputing and Analyzing Rare Variants in Association Studies

Trends Genet. 2015 Oct;31(10):556-563. doi: 10.1016/j.tig.2015.07.006.


Rare genetic variants may be responsible for a significant amount of the uncharacterized genetic risk underlying many diseases. An efficient approach to characterizing the disease burden of rare variants may be to impute them into existing large datasets. It is well known that the ability to impute a rare variant is dependent both on the array choice and number of individuals in the reference panel carrying that variant, although it is still unclear exactly how well imputation will work for rare variants. Here, we review the additional challenges that arise when imputing rare variants, looking at studies that have been able to impute rare variants, methods behind merging reference panels, approaches for imputing rare variants, and methods for analyzing rare variants.

Keywords: genome-wide association study; genotype imputation; rare variants.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Genome, Human
  • Genome-Wide Association Study / methods*
  • Genotype*
  • Genotyping Techniques
  • Humans
  • Polymorphism, Single Nucleotide / genetics*