PUBLIC RELEASE DATE:

4-Mar-2014

Contact: John Ascenzi ascenzi@email.chop.edu 267-426-6055 Children's Hospital of Philadelphia

Two recent genetic studies expand the list of genes involved with body fat and body mass index, and their connection to major Western health problems: heart disease, high blood pressure and diabetes. One study showed that higher body mass index (BMI) caused harmful effects on the risk of type 2 diabetes, high blood pressure and inflammation, while another study found gene signals linked to higher levels of body fat metrics, without showing causality.

"These findings are highly relevant to the obesity pandemic in the United States and many other countries," said geneticist Brendan J. Keating, D. Phil., of the Center for Applied Genomics at The Children's Hospital of Philadelphia. "Of course, much research remains to be performed to discover further genes involved in these complex metabolic diseases, and to better understand how to improve treatments."

Keating, who previously helped create a large gene-discovery tool called the Cardio Chip, was a co-leader of both studies, which drew on large international teams of scientists using DNA, laboratory and disease data from tens of thousands of people.

In the BMI research, published in the Feb. 6 issue of the American Journal of Human Genetics, Keating collaborated with clinical epidemiologist Michael V. Holmes, M.D., Ph.D., of the Perelman School of Medicine at the University of Pennsylvania. That study used a recently developed epidemiology tool called Mendelian randomization (MR) that rules out confounding factors such as behavioral and environmental influences 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.

Their analysis, concluded the authors, 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 Keating.

"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 Holmes. He added that, although the study showed that increasing BMI has an undesirable effect on cardiometabolic factors, interestingly, it did not show that higher BMI increased the risk of coronary heart disease.

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CHOP researcher finds more genetic signals linking weight and heart health risk factors

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