Family-based designs for genome-wide association studies

Nat Rev Genet. 2011 Jun 1;12(7):465-74. doi: 10.1038/nrg2989.


Association mapping has successfully identified common SNPs associated with many diseases. However, the inability of this class of variation to account for most of the supposed heritability has led to a renewed interest in methods - primarily linkage analysis - to detect rare variants. Family designs allow for control of population stratification, investigations of questions such as parent-of-origin effects and other applications that are imperfectly or not readily addressed in case-control association studies. This article guides readers through the interface between linkage and association analysis, reviews the new methodologies and provides useful guidelines for applications. Just as effective SNP-genotyping tools helped to realize the potential of association studies, next-generation sequencing tools will benefit genetic studies by improving the power of family-based approaches.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Data Collection / methods
  • Data Collection / standards
  • Data Collection / statistics & numerical data
  • Epidemiologic Research Design*
  • Family*
  • Genetic Linkage
  • Genome-Wide Association Study / methods*
  • Humans
  • Models, Genetic
  • Pedigree
  • Software Design