Newer tools for gene analysis show how variations in DNA are underlying factors affecting heart disease, a major worldwide cause of death and disability.

Investigators from The Children's Hospital of Philadelphia and the University of Pennsylvania used a recently developed tool called Mendelian randomization (MR), which analyzes genetic variations using a method that identifies genes responsible for particular diseases, independent of confounding factors - such as differences in behavior or environmental influences - that often limit the conclusions of epidemiology research.

"Now we are able to pinpoint gene signals that actually cause some of these conditions," said geneticist Brendan J. Keating, DPhil, of The Center for Applied Genomics. "Unraveling how genetic variants that influence lipid traits are related to heart disease risk is a step toward designing treatments."

Dr. Keating collaborated with University of Pennsylvania clinical epidemiologist Michael V. Holmes, MD, PhD. The researchers analyzed DNA data from 17 studies including more than 60,000 individuals, of whom more than 12,000 had experienced coronary heart disease, including heart attacks. The novelty of their approach lies in their use of a gene score MR analysis using individual participant data.

They confirmed that higher levels of low-density lipoprotein (LDL), the "bad cholesterol," were more likely to cause heart disease. But there were new results: High levels of triglyceride also caused higher risk of heart disease. At the same time, there was little evidence that higher levels of high-density lipoprotein (HDL), the "good cholesterol," had a protective effect.

"These findings are important in understanding which blood lipids cause heart disease and will enable clinicians to better target those lipids with drugs to reduce the risk of heart disease," Dr. Holmes said.

The investigators published their study in the European Heart Journal.