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To the Editor: The study of genetic risk factors for acute coronary syndrome (ACS) by Dr Morgan and colleagues¹ calls into serious question numerous reported associations between specific genes and ACS. Rather than finding this a reason to lose hope of identifying genetic contributions to ACS or other common diseases, we consider it a guide to improving such efforts, serving as a powerful reminder both of the limitations inherent to "candidate gene" approaches and the need for rigorous replication of research findings before clinical application. This article indicates the maturation of the study of the genetics of common complex disease.

Many of the studies that Morgan et al cite relied on educated but inherently biased guesses about genes that might be involved in ACS (candidate genes). These candidate genes were then used to look for associations between gene variants and disease in small populations. Although state-of-the-art a few years ago, . . . [Full Text of this Article]

W. Gregory Feero, MD, PhD
feerow@mail.nih.gov

Teri A. Manolio, MD, PhD; Alan E. Guttmacher, MD; Francis S. Collins, MD, PhD
National Human Genome Research Institute
National Institutes of Health
Bethesda, Maryland

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