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International study finds 21 genes tied to cholesterol levels

In a UCL-led study, published in the American Journal of Human Genetics, an international consortium of over 180 scientists report the identification of 21 new gene variants associated with cholesterol predictors of heart disease and metabolic disorders.

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The findings expand the list of potential targets for drugs and other treatments for lipid-related cardiovascular disease, a leading global cause of death and disability.

The International IBC Lipid Genetics Consortium analysed genetic data from over 90,000 individuals of European ancestry, covering approximately 50,000 DNA markers across 2,000 genes implicated in cardiovascular disease.

This study identified 21 novel genes associated with levels of low-density lipoproteins (LDL, or “bad cholesterol”), high-density lipoproteins (HDL, “good cholesterol”), total cholesterol (TC), and triglycerides (TG), as well as verifying 49 previously known signals. The researchers also found that some of the strongest signals appeared to have gender-specific effects and a more complex genetic architecture than previously thought.

Dr Fotios Drenos, UCL Institute of Cardiovascular Science, and Dr Brendan Keating of The Children’s Hospital of Philadelphia, are senior authors of the current study.

Dr Drenos said: “While each of the genetic variants has a small effect on the specific lipid trait, their cumulative effect can significantly add up to put people at risk for disease.

The cumulative effect of the genetic variants can significantly add up to put people at risk for disease.

Dr Fotios Drenos, UCL Institute of Cardiovascular Science

“This study underscores how international sharing of resources and datasets paves the way for robust, continuing discoveries of new and unexpected information from human genetic studies.”

Dr Keating added: “To date, this is one of the largest number of DNA samples ever used in a study for lipid traits, it clearly shows the value of using broad-ranging global scientific collaborations to yield new gene signals.”

Drs Drenos and Keating coordinated efforts among four main data collecting sites: the Center for Applied Genomics at The Children’s Hospital of Philadelphia; the UCL Institute of Cardiovascular Science; AMC, Amsterdam; and the Department of Cardiology at the University Medical Center, Utrecht.

The consortium is following this published work with a project to identify which of the loci reported directly cause disease, and how this knowledge can help in the development of novel drugs. The consortium will also devote its significant pooled resources to identifying interactions among genetic polymorphisms and biological markers of downstream cardiovascular disease.

Lead author Folkert Asselbergs, M.D., Ph.D., of University Medical Center, Utrecht, added: “Next to already established drug targets such as the LDL receptor and PCSK9, the current study identified 21 potential new targets for drug development that may be beneficial for the treatment of dyslipidaemia in the future. Our team of researchers are now initiating additional studies to investigate the impact of the found genes on cardiovascular disease.”

More than 30 organizations and agencies funded this study, including the British Heart Foundation, the Medical Research Council, the National Institutes of Health and the Wellcome Trust.

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Media contact: David Weston

Image caption: The main quad at UCL


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