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(Circulation. 2005;112:2081-2084.)
© 2005 American Heart Association, Inc.

Editorial

Eliminating the Improbable

Sherlock Holmes and Standards of Evidence in the Genomic Age

David Herrington, MD, MHS

From the Department of Internal Medicine/Cardiology, Wake Forest University School of Medicine, Winston-Salem, NC.

Correspondence to Dr David Herrington, Dept of Internal Medicine/Cardiology, Wake Forest University School of Medicine, Winston-Salem NC, 27157-1040. E-mail dherring@wfubmc.edu

Key Words: Editorials • genetics • myocardial infarction • cardiovascular diseases • women

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In 2003, Shearman and colleagues reported that a common variant in the estrogen receptor-alpha gene (ESR1 IVS1 –397 C allele) occurred more frequently in male subjects with myocardial infarction (MI) than in those free of MI.¹ The following year, Schuit et al described an association between the common haplotype containing the alternate (T) allele and MI, but only in women.² In this issue of Circulation, Koch et al³ report no association, in either men or women, between the ESR1 –397 T>C genotype or the common haplotypes containing this allele and MI. What does this collection of heterogeneous results tell us about genetic association studies in general and genetic variation in the estrogen receptor in particular; and how can we use this understanding to improve our ability to understand, treat, and prevent cardiovascular disease?

Article p 2138

Frequent failure to replicate initially promising genetic associations is a source of consternation and confusion for scientists and journal editors alike. Recent reviews of the literature indicate that 70% to 95% of reported genetic associations were not confirmed in subsequent studies.^4,5 It has been argued that false-positive reports of genetic associations distract energy and resources from valid lines of inquiry and erode the credibility of medical research. Some reputable journals now decline to publish genetic associations of complex disorders except in "exceptional circumstances" (http://www.jci.org/misc/jcipoli.pdf), and some scientists have argued that association studies are so unreliable that they should be abandoned altogether.⁶

"The temptation to form premature theories on insufficient evidence is the bane . . . [Full Text of this Article]

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