Replication in genetic studies of complex traits
This is a nice paper from 2004 that I just read for the first time. Even more important now given the frenzy over replication in association studies.
Sillanpää MJ, Auranen K. Replication in genetic studies of complex traits. Ann Hum Genet. 2004 Nov;68(Pt 6):646-57 [PubMed]
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.