HudsonAlpha Faculty Investigator Dr. Devin Absher is studying cardiovascular disease through a National Heart Lung Blood Institute (NHLBI) granted research program. The Atherosclerotic Disease, VAscular functioN, and genetiC Epidemiology (ADVANCE) study originated as a collaboration between Stanford University and Kaiser Permanente of Northern California.

The study began by recruiting a group of 3,600 Kaiser Permanente patients and determining the sequence of a handful of genes suspected to affect cardiovascular health.

Absher is participating in the first and second phases of the ADVANCE study. To begin, researchers conducted a genome-wide association study. This step involved the screening of more than 500,000 positions in the genetic code, called single nucleotide polymorphisms (SNPs), in samples from both cardiovascular disease patients and people without the disease. These small differentiations between the genomes of the two groups are potential markers for cardiovascular disease.

Under the first phase, Absher’s laboratory at HudsonAlpha tested the DNA markers in more than 1,000 human blood samples, with other laboratories adding to a total test group of 10,000 people.

In the second phase, which is ongoing, the data produced from the 10,000 analyzed individuals are being compiled and compared with one another to determine which shared SNPs could be heart disease indicators. Each ADVANCE collaborator will run statistical analyses of their data and nominate promising genes to further research. “Researchers gain better statistical power with combined data,” said Absher, “When we compile all of these data together, we will find the standouts from the whole study.”

Researchers will then design a custom microarray to test approximately 7,000 of the SNPs that are the best markers for cardiovascular disease. These microarrays will be used to test a second sample group of 12,000 to 15,000 individuals, an important step in verifying the data from the first phase. “The importance of genotyping as many individuals as possible is that larger numbers of samples reduce ‘noise’ in study results,” Absher said. “The results in phase one are only confirmed as promising targets after you limit the potential of a sample error in your initial study. Testing these potential indicators on more individuals will go further in proving the markers’ accuracy.”

According to Stanford University, the NHLBI-funded second phase of ADVANCE began October 1, 2006 and will run through July 31, 2009.