Genes linked to cholesterol and heart disease discovered

Cardiovascular disease (CVD) is the leading cause of death in Australia, with the National Health and Medical Research Council (NHMRC) estimating it costs Australia $5.9 billion in 2004-2005.

Combatting CVD is a matter of understanding its cause - both environmental and genetic - and determining effective ways to prevent and treat it.

These ends were significantly advanced today with the publishing of a study by an team of researchers from around the globe, including scientists from the Queensland Institute of Medical Research (QIMR), that uncovered 59 previously unknown genes that are linked to cholesterol levels in the blood.

Concentrations of three types of cholesterol - low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) and triglycerides - in blood plasma are among the most important risk factors for coronary artery disease.

The study involved screening over 100,000 individuals of European ancestry for genetic markers that were linked to cholesterol metabolism.

95 variants were found, of which 59 were new. Some of these variations don’t just influence normal lipid metabolism, but are linked to high likelihood of CVD.

It’s hoped this discovery will yield new targets for drug discovery that might be able to manipulate cholesterol metabolism and prevent CVD.

“We hope this kind of work will help identify new targets for drugs, and help us understand how fats are transported, deposited in blood vessels and broken down in the body,” said Dr John Whitfield from QIMR’s Genetic Epidemiology Laboratory, and co-author of the study.

“The ultimate would be a genetic test that can help tailor treatments to each specific person, for example, which drug and how much of that drug would be best.”

The study also lends support to genome wide association studies (GWAS), which were recently criticised for not being powerful enough to reveal the multitude of minute changes in the genome that can impact human disease.

“These studies demonstrate that GWAS – done at the proper scale and with the proper tools – remain a powerful approach to understanding biology and disease, and that even non-coding variants can have a clinical effect,” said Dr Kiran Musunuru, clinical and research fellow at Massachusetts General Hospital and research affiliate at the Broad Institute, who is a co-lead author the paper.

Like another recent study, it was found that it takes many small changes, even in some genes that have a very small effect, to account for the variability in susceptibility to CVD.

“Previous studies with only a few thousand people’s DNA typically identified the genes that have a large effect because they are the easiest ones to find,” said Whitfield. “By looking at 100,000 individuals’ DNA our study was more sensitive, allowing us to identify new regions.”

The paper was published in Nature today: doi:10.1038/nature09270.