Large international study finds 21 genes tied to cholesterol levels

October 11, 2012

In the largest-ever genetic study of cholesterol and other blood lipids, an international consortium has identified 21 new gene variants associated with risks of heart disease and metabolic disorders. 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 used the Cardiochip, a gene analysis tool invented by Brendan J. Keating, Ph.D., a scientist at the Center for Applied Genomics at The Children's Hospital of Philadelphia. Since its creation in 2006, researchers have used the Cardiochip to pinpoint gene variants in dozens of studies. The device contains approximately 50,000 across 2000 genes implicated in cardiovascular disease.

Keating and Fotios Drenos, Ph.D., of University College London, are senior authors of the current study, published today in the .

Comprising over 180 researchers worldwide, the consortium analyzed from over 90,000 individuals of . First the researchers used the Cardiochip in a discovery dataset of over 65,000 individuals from 32 previous studies. They then sought independent replication in other studies covering over 25,000 individuals, as well as in a previously reported study of 100,000 individuals.

From this meta-analysis, the consortium 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 known signals. The researchers also found that some of the strongest signals appeared to be gender-specific—some variants were more likely to appear in men, others in women.

Keating said, "To date, this is the largest number of 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."

Drenos added, "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." He continued, "This study underscores how international sharing of resources and datasets paves the way for robust, continuing discoveries of new and unexpected information from human ."

Keating and Drenos coordinated efforts among four main data coordinating sites: the Center for Applied Genomics at The Children's Hospital of Philadelphia; the Institute of Cardiovascular Sciences at University College London; 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 (single-base variations in DNA) 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."

Explore further: Genetic risks for type 2 diabetes span multiple ethnicities

More information: "Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci," American Journal of Human Genetics, published Oct. 11, 2012.

Related Stories

Genetic risks for type 2 diabetes span multiple ethnicities

February 9, 2012
A recent large and comprehensive analysis of 50,000 genetic variants across 2,000 genes linked to cardiovascular and metabolic function has identified four genes associated with type 2 diabetes (T2D) and six independent disease-associated ...

Largest-ever genome-wide study identifies genes for common childhood obesity

April 8, 2012
Genetics researchers have identified at least two new gene variants that increase the risk of common childhood obesity.

Recommended for you

Forgotten strands of DNA initiate the development of immune cells

September 21, 2017
Intricate human physiological features such as the immune system require exquisite formation and timing to develop properly. Genetic elements must be activated at just the right moment, across vast distances of genomic space.

Genome editing reveals role of gene important for human embryo development

September 20, 2017
Researchers have used genome editing technology to reveal the role of a key gene in human embryos in the first few days of development. This is the first time that genome editing has been used to study gene function in human ...

A piece of the puzzle: Eight autism-related mutations in one gene

September 19, 2017
Scientists have identified a hotspot for autism-related mutations in a single gene.

Scientists identify key regulator of male fertility

September 19, 2017
When it comes to male reproductive fertility, timing is everything. Now scientists are finding new details on how disruption of this timing may contribute to male infertility or congenital illness.

New assay leads to step toward gene therapy for deaf patients

September 18, 2017
Scientists at Oregon State University have taken an important step toward gene therapy for deaf patients by developing a way to better study a large protein essential for hearing and finding a truncated version of it.

Genomic recycling: Ancestral genes take on new roles

September 18, 2017
One often hears about the multitude of genes we have in common with chimps, birds or other living creatures, but such comparisons are sometimes misleading. The shared percentage usually refers only to genes that encode instructions ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.