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To the Editor: In their study of genetic risk factors for ACS, Dr Morgan and colleagues¹ reported negative results for the association between 84 genetic variants in 70 candidate genes for ACS in a case-control study (811 cases and 650 controls) restricted to white patients in the United States. Small effect sizes are expected for any candidate genetic variant involved in complex diseases such as ACS. Case-control studies are prone to numerous biases, which should be carefully considered particularly when small effect sizes are analyzed.

First, selection and misclassification biases in defining case and control status are major potential issues, for which no information was provided. Second, population stratification is of concern for large-scale studies,² and the self-reported race matching that was used to control for stratification may be inaccurate for weak genetic effects. This is because population substructure can be found even in a homogeneous isolate,³ and self-reported ethnicity . . . [Full Text of this Article]

Murielle Bochud, MD, PhD
murielle.bochud@chuv.ch

Arnaud Chiolero, MD, MSc; Fred Paccaud, MD, MSc
University Institute for Social and Preventive Medicine
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland

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