Identification of genetic variants that predispose to complex traits is a major goal of the biomedical investigators of the post‐Human Genome Project era, for whom the entire reference genome sequence and some of its frequent variants are a given. The most common form of genomic variation is the single nucleotide polymorphism (SNP). Indeed, SNP search has become a busy industry, as evidenced by the panoply of industrial methodologies. Although common diseases do not follow Mendelian inheritance patterns and the contribution of heredity to their pathogenesis may be hard to pinpoint, the genetic determinants of these complex traits are tractable. Knowledge of genetic predisposition will have broad consequences for preclinical diagnostics, preventive maneuvers, and therapeutic strategies. Coronary heart disease (CHD) constitutes the major public health burden of industrialized nations. It causes nearly half a million deaths in the United States yearly (making it the single leading cause of death in the United States) and accounts for 13.7% of total mortality worldwide (7,375,000 deaths, according to World Health Organization estimates for 1998). 1 CHD is multifactorial, and its progression is known to be influenced by risk factors such as cigarette smoking, elevated blood pressure, diabetes mellitus, obesity, aging, elevated serum LDL-cholesterol (LDL-C), and low-serum HDL cholesterol (HDL-C). Thus, plasma lipoprotein disturbances are among the most common biochemical abnormalities observed in patients with CHD. Moreover, many patients with CHD do not have markedly elevated LDL-C but rather have low HDL-C levels, either alone or accompanied by hypertriglyceridemia. An important goal is to determine why certain people are singled out to suffer low HDL-C and CHD. We have learned that both diseases can be affected by certain behaviors, such as exercise, mild alcohol consumption, and hormone (estrogen) replacement therapy, yet there seem to be strong genetic influences on the HDL-C level. According to theories of
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