DNA analysis validates link between short stature and heart risk

When Randy Newman sang his tongue-in-cheek tune about short people, he called attention to their little hands, little eyes and their little baby legs. Nowhere does his1978 hit mention that short people also have an increased risk of coronary artery disease.

But scientists have established this link in several large studies, and a new one shows that its not just a coincidence. Some of the genetic variants that cause people to have short stature also tend to boost their levels of bad cholesterol and triglycerides two risk factors for coronary artery disease.

After examining the DNA of 65,066 people with coronary artery diseasealong with that of 128,383 controls, researchers calculated that the risk for the condition rose by 13.5% for each 2.5-inch drop in height below the average. They also found thatLDL cholesterol andtriglycerides explain about one-third of this unfortunate relationship.

Theresults were published this week by the New England Journal of Medicine.

Coronary artery diseaseis a condition in which cholesterol and other substances in the blood form plaques that build up inside the vessels that supply the heart. This narrows the vessels and, over time, can weaken the heart muscle by depriving it of oxygen and nutrients. It also makes people vulnerable to a heart attack because its easier for an errant clot to cut off the blood supply altogether.

Coronary artery diseaseis the most common cause of death for men and women in the United States, according to the National Heart Lung and Blood Institute.

Some people had speculated that the link between shortness and coronaryartery diseasewas a matter of geometry. Tall people have bigger coronary arteries, and short people have smaller ones. Therefore, it stands to reason that any given amount of plaque has the potential to do more damage to someone with petite arteries than it does to someone with wider ones.

But the research team found a problem with this theory. Women have smaller-caliber arteries than men, they noted. That should mean that short women have the greatest risk of coronary artery disease. Instead, the researchers discovered that the genetic link between height and the diseasewas weaker in women than in men.

The researchers began their analysis by focusing on 180 places in the human genome that were shown to be associated with height in a 2010 study known as the Genetic Investigation of Anthropometric Traits, or GIANT. None of these 180 genetic variants had any previously known connection to the risk of coronary artery disease.

The researchers estimated how much a change in each of these height-related variants changed the odds of the diseaseamong thousands of people who had already participated in genome-wide association studies and clinical trials related to coronary artery disease. Most of the variants had little to no effect on their own. But once all of them were added together, the net effect was that the risk of coronary artery diseaserose as height fell.

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DNA analysis validates link between short stature and heart risk