In the midst of the growing epidemic of obesity, a group of School of Medicine researchers has dived into the human gene pool to look for solutions. The group recently identified genetic variations unique to obese men and are now embarking on a wider search to find additional genes linked to obesity.
“Stated in the most basic terms, we are studying why some people are fat and some are skinny,” said Ingrid B. Borecki, Ph.D., lead investigator and associate professor of biostatistics and of genetics.
“Our hypothesis is that it’s because they have variation in genes that affect weight gain.”
Recent national surveys have indicated that about two-thirds of adults in the United States are overweight and one-third are obese. Many scientists hold that this stems from a propensity for weight gain inherited from long-ago ancestors who adapted to recurring famines with a genetic makeup designed to store fat efficiently.
“At present, our consumption of nutrient-poor, calorie-rich foods is going up,” Borecki said. “Our physical activity is going down. The fact that we are gaining weight as a result is simply the environmental potentiation of our genetic predisposition.”
In August, the University research group reported in the American Journal of Human Genetics that it had identified genetic variants on chromosome 7 associated with obesity in men. The genetic variants are within the gene for leptin, a hormone that regulates body weight by inhibiting food intake and stimulating energy expenditure.
Now, the group has received a three-year, $1.7 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases to expand this investigation to find additional genetic variants influencing the tendency to become obese.
Preliminary work by the researchers has located a region on chromosome 13 that appears very likely to be linked to obesity. The region contains at least 15 genes, and the group will further analyze the region to determine precisely the relevant genetic variants.
The researchers will also seek additional genes associated with obesity on other chromosomes.
For their search, the researchers will use existing data from the Family Heart Study (FHS), a recent clinical project funded by the National Heart, Lung, and Blood Institute. The FHS gathered information about health and habits of hundreds of families.
Blood samples collected make it possible to determine the genetic makeup of each individual and compare genetic patterns to find variations linked to obesity.
“We’ll have mountains of data,” Borecki said. “It’s a whole new paradigm. We have to consider novel methods for trying to digest so much information and find patterns that make sense. So, biostatistics is the cornerstone of this study.”
The researchers will statistically account for lifestyle choices of people in the FHS initiative, including factors such as diet, smoking, drinking and physical activity. This will enable them to isolate the effects on obesity that are solely genetic.
“Once we’ve located the genetic variants found in obese people, we will look at the dataset to see if the same people also suffer from any of the diseases exacerbated by being overweight, diseases such as diabetes, lipid disorders, hypertension and coronary heart disease,” Borecki said.
“We can then look for common pathways — we can ask if any genes linked to obesity are involved in a process that leads to high blood pressure, for example.”
Ultimately, research that locates genes related to obesity will point to options for preventing and treating obesity and related diseases.
Collaborators on the project with Borecki include Michael A. Province, Ph.D., professor of biostatistics and of genetics; Richard Myers, Ph.D., of Boston University; and Kari North, Ph.D., of the University of North Carolina.