Today, 2 of 3 American adults suffer from obesity. Increasingly, many are reaching beyond diet and exercise to help stave off hunger and shed pounds — nearly 200,000 turned to bariatric surgery in 2009 as a means to achieve their weight loss goals.

But such surgery, which involves risky reconnections of the stomach and small intestines, is at times ineffective and can leave patients permanently dependent on calcium, iron, additional dietary supplements, and more susceptible to hernias, ulcers and other conditions.

Worst of all, for many the effects of surgery are fleeting, as they often regain the weight over a period of time.

In an effort to better understand how one’s genetic make up influences weight gain and its many effects on the human body, TGen scientists have partnered with Geisinger Health System of Danville, Pennsylvania in a study potentially involving more than 4,000 patients. A disease, obesity stems from more than overeating or lack of exercise; research has shown there is often an underlying genetic component leading to excess weight gain. This study is the first planned as part of a recently signed strategic research agreement between TGen and Geisinger that provides for a focused look at the gaps in clinical medicine where biomedical research can make a difference.

Leveraging Geisinger’s wealth of clinical information — nearly 20 years worth of electronic health record data— the study will focus on identifying genetic markers that will enable physicians to determine who might be the best candidates for Roux-en-Y gastric bypass (RYGB), the most common bariatric procedure.

This long-term study, expected to last at least five years, and probably longer, also could assist in the development of new anti-obesity drugs, and lead to personalized weight-loss therapies.

“This study is unique in that a wealth of clinical and behavioral information is available on each patient,” said Dr. Johanna DiStefano, Director of TGen’s Diabetes, Cardiovascular and Metabolic Diseases Division. “Such information is critical for unraveling the links between genetic susceptibility and environmental exposures that determine individual risk of regaining weight following a RYGB procedure.”

The RYGB study is the first of many planned under an alliance announced in February between TGen and Geisinger.

“We have a common mission to make major advances against complex diseases, and are working together on strategies for applying the advanced genomic profiling technologies to individualized health care delivery, with an initial focus on diabetes, obesity and oncology,” said Dr. Jeffrey Trent, TGen’s President and Research Director.

The RYGB study will examine the genomes of 2,000 Geisinger patients, identifying upwards of 1 million variables in their DNA that could indicate an association with regaining weight after RYGB surgery.

In addition, as many as 2,000 controls (or non affected patients) will be examined, including patients from Geisinger, and study collaborators at Massachusetts General Hospital in Boston and Temple University’s Center for Obesity Research and Education in Philadelphia.

“Given our unique research structure and a patient population that overwhelmingly supports cutting-edge research, I am confident our partnership with TGen will allow us to test and apply new clinical translation theories to obesity and other areas of patient care,” said Glenn D. Steele, Jr., M.D., Ph.D., Geisinger’s President and CEO. “I look forward to the results of this first study, as I am confident we can greatly improve the outcomes for individuals coping with obesity and its many associated complications.”

More Americans are moving to RYGB after seeing only modest and short-term results from diet and exercise, even those adhering to disciplined weight loss efforts.

In contrast, bariatric surgery — especially RYGB — yields more substantial and sustained weight loss. It is a more effective therapy for long-term weight loss in morbidly obese patients, and also as a surgical therapy for those suffering from type 2 diabetes. RYGB is the bariatric operation least likely to result in nutritional difficulties.

The amount of weight loss with RYGB varies. Clinical and physiological characteristics have so far failed to distinguish individuals who will maintain weight loss following bariatric surgery from those who will not.

“This study is especially innovative in that it seeks to incorporate environmental factors that interact with genetic variants to manifest a particular response, a complexity seldom examined in these kinds of studies,” Dr. DiStefano said.

The knowledge gained from this study ultimately may help physicians decide which patients are suitable candidates for RYGB, and which are not.