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Genetic variations affect weight, response to exercise

by April Sutton

Molly Bray, Ph.D.

Looking at Molly Bray, Ph.D., you'd never suspect that she was a chubby kid who hated being overweight.

"I was a fat kid and a chunky teenager, and I think that is why I became so interested in obesity," said Bray, an associate professor of pediatrics at the U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center at Baylor College of Medicine. This is a joint program with Texas Children's Hospital.

In 1990, she went to the University of Houston to obtain her master's degree in exercise physiology, hoping ultimately to open an aerobics studio where chubby kids and teens could work out without feeling self conscious. But Bray says she was detoured by the "research bug" and decided to continue her education and obtain her doctorate.

"I'd never done anything other than whole human physiology before attempting my Ph.D.," Bray said. "I decided to study genetics because I'd had very good training in statistical analysis and felt comfortable with the analytical approaches being used by geneticists to study disease."

Bray's research is aimed at getting to the very base of obesity and trying to figure out why some Americans waistlines are plumping up no matter how hard they exercise and eat a balanced diet.

TIGER study

The Training Interventions and Genetics of Exercise Response study is a 30-week exercise program designed to investigate how genetic variation influences levels of body fat and fitness. More than 1,500 University of Houston students and staff will ultimately be recruited to participate in the five-year study.

"The TIGER study evolved from a dream that I had while in graduate school," Bray said. "I wanted to combine my background in exercise with my training in genetics and now I'm finally seeing my dreams come to life."

Participants complete 30 minutes of aerobic exercise three days a week and receive information on aspects of fitness and exercise. Researchers involved in the study will analyze the effect of variation in genes involved in fat tissue formation, muscle development and growth, energy metabolism and eating behavior in relation to changes in body mass and composition, fat distribution, obesity status and heart rate at the completion of the program.

"This is the largest and most ethnically diverse study ever conducted that looks at how genes may influence a person's response to exercise," said Bray. "If we can determine the genes involved, then we might be able to prescribe an exercise program that fits each person's individual needs, one that really works and is easier for them to maintain."

Other studies

Before coming to the CNRC in October of 2004, Bray worked at The University of Texas Health Science Center at Houston for seven years. While there, she worked on a project called Gene-Environment Interaction in Complex Disease in which she collected information on gene variations among almost 16,000 people who had been involved in a study of heart disease risk involving the narrowing of arteries by deposits of material called plaque. From the data, Bray and her colleagues will analyze DNA sequence variants for their association with obesity and body size.

She is also working with other BCM doctors to investigate which genes are related to morbid obesity, as well as how and if these genes play a role in a patient's response to the gastric bypass surgery. The study, still in the developmental phase, will include children and adult participants.

"Gastric bypass patients are an interesting group because they almost certainly have a genetic predisposition for obesity," Bray said. "This project will include a whole genome scan of genetic variation in obese cases and lean controls."

The researchers plan on submitting their grant for the project in February, but in the meantime they are already looking at changes in gene expression in liver biopsies collected before and after surgery from adolescent gastric bypass patients.

Obesity as an issue

Obesity is one of the most profound public health problems of today. Bray doesn't have the answer, but her work is designed to improve understanding of how the problem originates.

"I see how obese people struggle on so many levels," she said. "Physically it's hard to be a big person, and emotionally they deal with a lot of prejudices. People often assume that obese people are just lazy and greedy, but it is harder for some people to lose and/or maintain a healthy weight than others, and that difficulty may be related to their genetic makeup."

Bray says she hopes to identify the genes that predispose individuals to obesity, in order to identify those who are at risk earlier or to intervene more aggressively with those who are already obese.

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