In Reply: We note that all writers indicated broad agreement with our conclusion of the need for robust validation of genetic risk factors to provide convincing evidence that a true genetic risk factor has been identified. We agree with the comments of Dr Feero and colleagues that unbiased studies of whole genome association are likely to lead to important discoveries. Recent findings have illustrated the power of this approach and underscore the frequent need for large sample sizes and replication cohorts to achieve meaningful and convincing results.1-5 Of interest is that the variants identified in these studies show consistent replication of the identical alleles in diverse cohorts.
Morgan TM, Krumholz HM, Lifton RP, Spertus JA. Validity of Reported Genetic Risk Factors for Acute Coronary Syndrome—Reply. JAMA. 2007;298(15):1757–1759. doi:10.1001/jama.298.15.1759-a
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