Background
Genetic association studies are widely used in biomedical research and yet only a
minority of positive findings stand the test of replication. I explored the capacity
of association studies to produce false positive findings and the impact of various
definitions of replication.
Methods
Genetically realistic simulation data of a typical genotyping/analytic approach for
10 single nucleotide polymorphisms (SNPs) in COMT, a commonly studied candidate gene.
Results
Candidate gene studies like those simulated here are highly likely to produce one
or more false positive findings at α ≤ .05, the pattern of findings can often be “compelling”
or “intriguing,” and false positive findings propagate and confuse the literature
unless the definition of replication is precise.
Conclusions
Findings from single association studies constitute “tentative knowledge” and must
be interpreted with exceptional caution. For the association method to function as
intended, every statistical comparison must be tracked and reported, and integrated
replication is essential. Precise replication (the same SNPs, phenotype, and direction
of association) is required in the interpretation of multiple association studies.
Key Words
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Article info
Publication history
Published online: March 12, 2007
Accepted:
November 14,
2006
Received in revised form:
November 7,
2006
Received:
September 22,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
