Replication in genetic studies of complex traits

Ann Hum Genet. 2004 Nov;68(Pt 6):646-57. doi: 10.1046/j.1529-8817.2004.00122.x.


Disappointments in replicating initial findings in gene mapping for complex traits are often attributed to small sample sizes and inadequate techniques to determine the threshold value. This is clearly not the whole truth. More fundamental reasons lie in the inherent heterogeneity related to disease, including genetic heterogeneity, differences in allele frequencies, and context-dependency in genetic architecture. There are also other reasons related to the data collection and analysis. Replication may remain a source of frustration unless more emphasis is put on controlling these sources of heterogeneity between studies.

Publication types

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

MeSH terms

  • Bayes Theorem
  • Chromosome Mapping / statistics & numerical data*
  • Gene Frequency
  • Genetic Heterogeneity*
  • Humans
  • Models, Genetic
  • Research Design*