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To the Editor: Genetic association studies of common traits are frequently limited by failures of replication and insufficient correction for multiple testing.^1-2 Dr Smith and colleagues³ evaluated the association of 24 candidate genes with the risk of venous thrombosis. I have a number of concerns about the use in this study of the false discovery rate (FDR) q value, an emerging statistic that may assist in evaluation of the validity of genetic association findings.^4-5

First, the q value was applied to all tests of significance (as in Table 2 of the article). The FDR applies only to positive findings—ie, "discoveries."^4-5 If a hypothesis test fails to find an association, the FDR is meaningless, because those results are either false negative or are not truly associated with the study end point. With  = .05, results for only 3 of the 25 tests in Table 2 merit calculation of the FDR.

Second, no . . . [Full Text of this Article]

Benjamin D. Horne, PhD, MPH
benjamin.horne@intermountainmail.org
Cardiovascular Department
LDS Hospital, Intermountain Medical Center
Salt Lake City, Utah

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Genetic Association Studies and False Discoveries—Reply
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