October 8, 2013

DNA Study by Cristen Willer and colleagues points to new heart drug targets and a key role for triglycerides.

" A global hunt for genes that influence heart disease risk has uncovered 157 changes in human DNA that alter the levels of cholesterol and other blood fats – a discovery that could lead to new medications.

The huge scan of genetic variations linked to blood lipid levels used an advanced device called a Metabochip. Each of the changes points to genes that can modify levels of cholesterol and other blood fats and are potential drug targets. Many of the changes point to genes not previously linked to blood fats, also called lipids. A surprising number of the variations were also associated with coronary artery disease, type 2 diabetes, obesity, and high blood pressure.

The research also reveals that triglycerides – another type of blood lipid – play a larger role in heart disease risk than previously thought.

The results, published in a paper and a letter appearing simultaneously in the journal Nature Genetics, come from the Global Lipids Genetics Consortium -- a worldwide team of scientists who pooled genetic and clinical information from more than 188,000 people from many countries and heritages.

The analysis of the combined data was led by a team from the University of Michigan Medical School and School of Public Health. They used sophisticated computing and statistical techniques to search for genetic variations that modify blood lipid levels.

The results increase by more than a third the total number of genetic variants linked to blood lipids. All but one of the variants associated with blood lipids are near stretches of DNA that encode proteins.

“These results give us 62 new clues about lipid biology, and more places to look than we had before,” says Cristen Willer, Ph.D., the lead author of one paper and an assistant professor of Internal Medicine, Human Genetics and Computational Medicine & Bioinformatics at the U-M Medical School. “Once we take the time to truly understand these clues, we’ll have a better understanding of lipid biology and cardiovascular disease -- and potentially new targets for treatment.”

But, cautions senior author and U-M School of Public Health Professor Gonçalo Abecasis, Ph.D., it will take much further work to study the implicated genes and to find and test potential drugs that could target them. The consortium’s “open science” approach will include publishing further detail online for other researchers to use freely toward this goal.

A further analysis of the dataset, published as a letter with lead author Ron Do, Ph.D. and senior author Sekar Kathiresan, M.D. from the Broad Institute and Massachusetts General Hospital, suggests triglyceride levels have more impact on coronary artery disease risk than previously thought."

Cristen J. Willer, Ph.D.

Cristen Willer, Ph.D.

Professor of Internal Medicine
Professor of Human Genetics
Professor of Computational Medicine and Bioinformatics
734-647-6018