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The article presents a study seeking to determine whether genetically reduced high-density lipoprotein (HDL) due to heterozygosity for loss-of-function mutations in the adenosine triphosphate-binding cassette transporter A1 (ABCA1) gene causes increased risk of ischemic heart disease (IHD). The design and setting of the studies, which were drawn from the general population in Copenhagen, Denmark, are described. The outcomes measured the level of HDL cholesterol in the population, cellular cholesterol efflux, and the link between IHD, HDL, and genotype. Results suggest that lower levels of HDL related to loss-of-function mutations in the ABCA1 gene were not associated with an increased risk of IHD.