A New Era of Cardiovascular Disease Epidemiology

Abstract

CARDIOVASCULAR EPIDEMIOLOGY HAS A RICH, COLlaborative, and productive history. Beginning in 1948, the Framingham Heart Study was instrumental in identifying, for instance, high blood pressure and dyslipidemia as major risk factors for coronary heart disease and stroke. Subsequent clinical trials identified safe and effective treatments for these conditions. In the last several decades, the widespread use of medications for hypertension and dyslipidemia have prevented or delayed the onset of cardiovascular disease for millions of US residents. At the 60th anniversary of the Framingham study, a new approach to cardiovascular disease epidemiology is about to be tested. In October 2007, data from approximately 9000 Framingham participants, not only extensive phenotype data but also 500 000 single nucleotide polymorphisms (SNPs) from a whole-genome scan on each individual, became accessible to the scientific community under the SHARe (SNP Health Association Resource) program. Scientists who meet standards that include approval by an institutional review board, human subjects training, computer security, and design and analysis plans will receive the Framingham genotype and phenotype data. These data will be available to all scientists, including the Framingham investigators, at the same time. Non-Framingham study scientists who receive data may begin analyses immediately, but they must agree to a 1-year moratorium before submitting manuscripts to journals. In recognition of the fundamental scientific incentive of publishing the first analysis of one’s own data, the Framingham study investigators, many of whom spent years acquiring the phenotype data, are not bound by the moratorium and may submit manuscripts at any time after the release of the whole-genome data. SHARe represents a novel resource that allows the scientific community ready access to this large complex data set and, thus, seeks to enhance the breadth and scale of scientific output from this landmark epidemiological study. In a similar program, the Candidate-gene Association Resource (CARe) Project will assay 55 000 SNPs in 2000 cardiovascular-candidate genes. Data-release procedures similar to those used in SHARe will make available to the scientific community both the CARe genotype and extensive phenotype data on about 50 000 participants in 9 National Heart, Lung, and Blood Institute (NHLBI)–funded cohorts in the spring of 2008. SHARe and CARe are indeed public resources. The expectation is that the widespread availability of these data to the scientific community at large will accelerate high-quality scientific findings in genetics. The approach of making data widely available resembles the model used to assemble the human genome. Sequencing the human genome represented an astonishing scientific and technologic achievement that used a hierarchical shotgun sequencing strategy. DNA was fragmented, fragments were sequenced, and the sequenced parts were assembled. In the human genome project, sequenced fragments were placed immediately on the Web, and various groups worked to assist in their assembly. The genome data consist of 1 of 4 base pairs in a specific order; and the goal, which was computationally complex, was to deduce the proper order of many modest-sized strings of base pairs. The release of sequence data on the Web not only made publicly funded research data immediately available but also advanced the pace of describing the structure of the human genome. The effort to generalize from the genome assembly of basepair data to the epidemiological analyses of genotypephenotype data represents a bold experiment. The release of the Framingham data to the scientific community takes advantage of quality-control efforts that were in place for data collection but abandons the quality-control efforts that were in place for data analysis and manuscript production in favor of widespread data access. The quantity and the quality of the science that emerges from this “genome” experiment remain to be seen. Prior experience with similar efforts may provide some clues. All the major NHLBI cohort studies have already made limited access data sets (LADs) available to the scientific community. For instance, LADs for the Atherosclerosis Risk in