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To the Editor: The study by Dr Morgan and colleagues¹ maintained that aside from the -fibrinogen gene FGB (P = .03), none of the other 85 gene variants previously associated with ACS could be replicated in their study. However, we note that the most significant association with a variant of thrombospondin 2 (THBS2) (P = .002) was overlooked despite replicating an association^2-3 with respect to allele and magnitude.

While we agree with the main conclusion of the study that it is premature to be using these genetic markers in clinical care, we found the methodology and conclusions to be oversimplified. Not considering the THBS2 results a replication highlights a more crucial matter: the subjectivity in deciding what constitutes a replication. Should we consider minor alleles that have apparent protective effects as invalid? Similarly, should we discount genes for which the original variant does not produce a significant association, but . . . [Full Text of this Article]

Jeanette J. McCarthy, PhD
jeanette.mccarthy@duke.edu
Duke Institute for Genome Sciences & Policy
Duke University Medical Center
Durham, North Carolina

Eric J. Topol, MD
Scripps Translational Science Institute
La Jolla, California

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