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Fifteen new genetic regions associated with CAD identified
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In the largest genetic study of CAD to date, researchers for the CARDIoGRAMplusC4D Consortium have identified 15 genetic regions newly associated with the disease. This research brings the total number of validated genetic links with CAD discovered through genome-wide association studies to 46, according to a press release.
The research team further identified 104 independent genetic variants that are also likely to be associated with CAD.
“Together, these variants explain approximately 10.6% of CAD heritability,” Panos Deloukas, PhD, and the consortium wrote in Nature Genetics.
More than 170 researchers were involved in the meta-analysis combining genetic data from more than 190,000 participants. About one-quarter of the genetic regions associated with CAD or MI were also found to be strongly associated with cholesterol, especially elevated levels of LDL. An additional 10% were linked to high BP, according to information in the release.
“Perhaps the most interesting results of the study show that some people may be born with a predisposition to the development of coronary atherosclerosis because they have inherited mutations in some key genes related to inflammation,” Themistocles (Tim) Assimes, MD, PhD, a Stanford assistant professor of medicine, stated in a press release. “There has been much debate as to whether inflammation seen in plaque buildup in heart vessels is a cause or a consequence of the plaques themselves. Our network analysis of the top approximately 240 genetic signals in this study seems to provide evidence that genetic defects in some pathways related to inflammation are a cause.”
“The signals that do not point to known risk factors may be pointing to novel mechanisms of disease,” Assimes stated. “It is imperative that we quickly gain a better understanding of how these regions are linked to heart disease, as such understanding will greatly facilitate the development of new drugs to prevent heart disease.”
This meta-analysis builds on previous research published in Nature Genetics in 2011. In that study, researchers examined 2.5 million single nucleotide polymorphisms from 14 genome-wide association studies, which yielded discovery of 13 new gene regions associated with heart disease.
For the new study, researchers added to the 2011 study data, for a total of 41,513 patients with heart disease and 65,919 controls. The researchers used a specialized genetic chip that incorporated only the top signals from the original meta-analysis of the initial 14 genome-wide association studies.
“We went beyond traditional genetic association studies to explore likely genetic signals associated with the disease and to use the information to identify biological pathways underlying CAD,” Deloukas, co-lead author from the Wellcome Trust Sanger Institute, Australia, stated in a release.
According to Deloukas, the “next step is to design new analyses to also test rarer variants to provide a full catalog of disease associations that in the future could identify individuals most at risk of a heart attack.”
For more information:
The CARDIoGRAMplusC4D Consortium. Nat Genet. 2012;doi:10.1038/ng.2480.
Disclosure: The researchers report no relevant financial disclosures.