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STATE-OF-THE-ART PAPER

Genetic Approaches to Coronary Heart Disease

Center for Human Nutrition and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas.

Manuscript received November 29, 2005; revised manuscript received May 22, 2006, accepted June 20, 2006.

^_* Reprint requests and correspondence: Dr. Jonathan C. Cohen, Center for Human Nutrition, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390. (Email: jonathan.cohen{at}utsouthwestern.edu).

Developments in high-throughput genotyping have progressed to the point where genome-wide association studies are becoming practical. Multistage designs involving large numbers of sequence variants (300,000) and relatively large samples sizes (several hundred cases and control subjects) will be essential to reliably detect alleles with appreciable effect sizes (2-fold increase in relative risk). Direct sequencing of candidate genes in cases and control subjects provides an alternative approach that can reveal low-frequency alleles that influence disease susceptibility. Ultimately, the outcome of both approaches will depend on the genetic architecture of coronary heart disease.

Abbreviations and Acronyms   CHD = coronary heart disease   LDL-C = low-density lipoprotein cholesterol   SNP = single nucleotide polymorphism

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