09 July 2020
Raft of genetic loci linked to heart disease
Published online 5 December 2012
Coronary heart disease (CHD), also known as coronary artery disease (CAD), is the leading cause of death worldwide. Although several lifestyle factors including smoking, diabetes and obesity are known risk factors, studies have shown that 40–50% of susceptibility to the disease is down to a person's genes1.
Previously, genome-wide associations studies (GWAS) found 31 genetic loci associated with risk for CHD. The biggest GWAS yet by an international consortium, CARDIoGRAMplusC4D, has now found another 15 loci linked to disease susceptibility, and publish their findings in Nature Genetics2.
The team of 180 scientists from across the world, including Pierre Zalloua of the Lebanese American University, Beirut, also identified 104 other independent genetic variations very likely to be involved.
Altogether, these gene variants only account for 10.6% of CAD heritability. "For most of us, genetic risk to CAD is defined by many genetic variants, each of which has a modest affect," says Panos Deloukas of the Wellcome Trust Sanger Institute in Cambridge, UK, one of team leaders.
The researchers performed a network analysis with 233 candidate genes to identify the biological pathways underlying CHD. Lipid metabolism pathways were most prominently linked to CHD risk, and networks underlying inflammation were also strongly associated. "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," explains Nilesh Samani of the University of Leicester, another lead author.
"Our next step is to design new analyses to also test rarer variants to provide a full catalogue of disease associations that in the future, could identify individuals most at risk of a heart attack," adds Deloukas.
- Peden, J.F. & Farrall, M. Thirty-five common variants for coronary artery disease: the fruits of much collaborative labour. Hum. Mol. Genet. 20 R2, R198-R205 (2011).
- The CARDIoGRAMplusC4D Consortium. Nature Genetics. doi:10.1038/ng.2480 (2012).