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Studies Find Genes Linked to BMI, Cardiovascular Health

Published on April 17, 2014 in Cornerstone Blog · Last updated 6 months ago


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Two recent studies expand the list of genes associated with body fat and body mass index (BMI), and their connection to heart disease, high blood pressure, and diabetes. One study showed higher BMI caused harmful effects on the risk of type 2 diabetes, high blood pressure, and inflammation, while a second investigation found gene signals linked to higher levels of body fat metrics.

According to the CDC, heart disease causes approximately 600,000 deaths each year in the United States, and 67 million adults have high blood pressure (which is associated with increased rates of heart attack, heart failure, and stroke). For its part, diabetes is the 7th most common cause of death, and nearly 12 percent of American adults over 20 years of age are living with diabetes.

“These findings are highly relevant to the obesity pandemic in the United States and many other countries,” said the Center for Applied GenomicsBrendan J. Keating, DPhil, who co-led both studies.

Lowering BMI Could Improve Cardiovascular Health

In the BMI investigation, published recently in the American Journal of Human Genetics, Dr. Keating collaborated with clinical epidemiologist Michael V. Holmes, MD, PhD, of the Perelman School of Medicine at the University of Pennsylvania. That study made use of a recently developed tool called Mendelian randomization (MR) that allows researchers to construct genetic risk scores for specific traits of interest.

The study team analyzed eight population cohorts including over 34,000 individuals of European descent, of whom over 4,400 had type 2 diabetes, over 6,000 had coronary heart disease and over 3,800 had a previous stroke.

“This study is the first to use this emerging MR technique with a combination of genetic markers known to impact BMI, to assess the causal relationship of BMI and a comprehensive repertoire of traits,” said Dr. Holmes.

The authors concluded that their analysis supports the importance of BMI in regulating cardiometabolic traits and the risk of type 2 diabetes. “Our findings suggest that lowering BMI is likely to result in multiple reductions of cardiovascular traits: in blood pressure, inflammation, fasting glucose and insulin, and in the risk of type 2 diabetes,” said Dr. Keating.

Body Fat Genetic Signals Discovered

Dr. Keating also co-led a second study, published in Human Molecular Genetics, that analyzed genes associated with central adiposity. Measures of central adiposity, or body fat, can be derived using waist circumference and waist-to-hip ratio.

Keating’s co-senior author was Kira C. Taylor, PhD, MS, of the University of Louisville. The study team performed a meta-analysis in over 57,000 subjects of European ancestry, then validated their results in even larger numbers from independent studies.

This study discovered three novel genetic signals associated with central adiposity, in the genes TMCC1, HOXC10, and PEMT. In addition, the team found two more novel genetic signals, in the SHC1 and ATBDB4 genes, which were only observed in women.

“Previous research has reported different gene variants operating between men and women related to adiposity,” said Dr. Keating. “This gives us initial clues of the genes involved with sex-specific body shapes. Future research using these findings may yield insight into the actual biological mechanisms that dictate why males and females have different body distributions of fat deposits.”

The adiposity study showed an association, not a causal role, for the genetic signals, with other signals yet to be discovered using even larger sample sizes. Several of the genes are in regulatory regions, Dr. Keating noted. While additional work is needed to tease out the biology of these signals, but the first steps of identifying genes underpinning these traits has been accomplished, Dr. Keating added.