International Gene Mapping Study Identifies More Genes Linked to Cardiovascular Disease Risk

A large study focusing on the genetics of cardiovascular disease (CAD) identified several significant molecular pathways mapping to networks linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD.

The study was carried out under the aegis of the CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome-wide Replication and Meta-analysis plus The Coronary Artery Disease) consortium, hosted by the Wellcome Trust Sanger Institute (Hinxton, United Kingdom). This consortium represents a collaborative effort to combine data from multiple large-scale genetic studies to identify risk loci for coronary artery disease and myocardial infarction.

The latest study from the CARDIoGRAMplusC4D Consortium combined the efforts of 180 researchers from countries across Europe (United Kingdom, Germany, Iceland, Sweden, Finland, The Netherlands, France, Italy, and Greece) as well as Lebanon, Pakistan, Korea, USA, and Canada. These laboratories analyzed DNA samples from more than 60,000 CAD cases and 130,000 normal controls.

Results published in the December 2, 2012, online edition of the journal Nature Genetics identified 15 genetic regions newly associated with the disease, bringing to 46 the number of regions associated with CAD risk. A further 104 independent variants strongly associated with CAD were found, which account for approximately 10.6% of inherited CAD genes. The four most significant pathways mapping to these networks were linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD.

Of the 46 genome-wide significant lead single-nucleotide polymorphisms (SNPs), 12 showed a significant association with a lipid trait, and five showed a significant association with blood pressure, but none was significantly associated with diabetes.

"The importance of the work is that while some of the genetic variants that we have identified work through known risk factors for CAD such as high blood pressure and cholesterol, many of the variants appear to work through unknown mechanisms," said senior author Dr. Nilesh Samani, professor of cardiology at the University of Leicester (United Kingdom). "Understanding how these genetic variants affect CAD risk is the next goal and this could pave a way to developing new treatments for this important disease."

Related Links:
Wellcome Trust Sanger Institute
University of Leicester