Researchers identify core traits strongly linked to eating disorders affecting 11 million Americans

September 12, 2005
CHAPEL HILL — An international team of researchers led by investigators at the University of North Carolina at Chapel Hill and the University of Pittsburgh School of Medicine has identified six core traits that appear to be linked to genes associated with two common eating disorders: anorexia and bulimia nervosa.Approximately 10 million females and 1 million males nationwide are affected by either anorexia or bulimia.

The new findings, which appear in two papers published in the current online edition of the American Journal of Medical Genetics Part B, bring researchers closer to identifying specific genes and also may have implications for genetic studies of other complex genetic disorders.

These six core traits are: “obsessionality” (a form of perfectionism); age at menarche (menstruation); anxiety; lifetime minimum body mass index (BMI), a measure of body size based on height and weight; concern over mistakes; and food-related obsessions.

The studies also found that minimum BMI, concern over mistakes, age at menarche and food-related obsessions appeared to be more closely linked to bulimia, whereas obsessionality and anxiety appeared to be more closely linked to anorexia, suggesting that, although closely related, the two conditions have some underlying differences.

The research team culled the six core traits from a list of more than 100 behaviors and personality traits believed to contribute to development of anorexia and/or bulimia. These traits and individual histories involving almost 400 individuals with eating disorders recruited into the study were assessed through structured interviews and standardized tests.

Historically, anorexia and bulimia have been considered closely related disorders or manifestations of the same disorder that is influenced primarily by social and cultural norms, such as society’s emphasis on thinness and being attractive.

In recent years, however, research has increasingly pointed to substantial biological and genetic contributions as well.

“The research underscores how critically important genetics are in the origins of eating disorders,” said Dr. Cynthia M. Bulik, director of the Eating Disorders Program at UNC’s School of Medicine and lead author of the first paper. Bulik also is the William and Jeanne Jordan distinguished professor of eating disorders in the school’s department of psychiatry and professor of nutrition, a department jointly housed in UNC’s schools of medicine and public health.

Anorexia nervosa is characterized by the relentless pursuit of thinness and obsessive fears of being fat. Self-starvation, extreme weight loss and related medical complications that accompany the disorder can result in death.

In contrast, bulimia nervosa is characterized by recurrent episodes of binge eating followed by self-induced vomiting, fasting, excessive exercise or misuse of laxatives or other substances, to prevent weight gain.

Although people with bulimia usually maintain a normal weight, they, too, often have an obsessive fear of gaining weight, express a constant desire to lose weight and report feeling intensely dissatisfied with their bodies.

Studies of families have shown that individuals with a mother or sister who has suffered from anorexia are 12 times more likely than people without such a family history to develop the disorder and have four times the risk for developing bulimia. Studies also have consistently linked anorexia and bulimia to a cluster of moderately heritable personality and behavioral traits.

However, identifying the genetic variations in the human genome that cause these traits has, until now, been a complicated and cumbersome process, said Dr. Bernie Devlin, associate professor of psychiatry and human genetics at the University of Pittsburgh School of Medicine and a senior author of both studies.

“What we did new in these studies was to combine statistical analysis with expert opinion to come up with a core set of traits that were strongly associated with these two disorders to use in further analyses.”

Dr. Walter H. Kaye, professor of psychiatry at the University of Pittsburgh School of Medicine and head of this international group of clinicians, researchers and statisticians attempting to understand the genetic causes of eating disorders, agreed that this approach presents a major step forward. “This is really a pioneering study, and we are very lucky to be able to bring the kinds of statistical and clinical expertise we have to the analysis of our data.”

In the second of the two papers, the investigators conducted what is known as linkage analyses on these six traits to determine whether or not they could be used to pinpoint regions of the human genome that increase an individual’s risk for developing these two eating disorders.

To their surprise, the analyses produced a pattern of significant linkage signals for bulimia but a less significant and somewhat different pattern of signals for anorexia.

Based on their findings, the investigators concluded that genes on chromosomes 10, 14 and 16 significantly affect risks for developing bulimia, but have a lesser impact on risks for anorexia. They found less significant, but still suggestive signals from other regions of the genome that were more closely linked to anorexia.

Interestingly, when they combined the data from anorexic and bulimic individuals and again conducted the linkage analyses, all of the significant genetic signals for bulimia were slightly or substantially lessened, while some of the suggestive signals for anorexia were amplified.

Although it is possible that combining the data reduced the significant signals for bulimia because they were merely “false positives,” the investigators inferred instead that anorexia and bulimia differ at a fundamental biological and genetic level.

The region on chromosome 10 that produced significant linkage with bulimia but not anorexia overlaps substantially with regions of chromosome 10 that previously have been linked with obesity, the researchers found.

This finding is consistent with other studies and observations, Bulik said.

“If you look at families with a high incidence of bulimia, you also find a high incidence of obesity,” she added. “However, if you look at families with a high incidence of anorexia, you don’t find a high incidence of obesity. So, although these are two genetically related disorders, there clearly appear to be some differences between them.”

The investigators cautioned that their findings require further replication in larger samples of individuals with anorexia and bulimia, but they suggested that their methods have much broader applications. In particular, they said, their approach can be applied and/or adapted to linkage studies of other complex conditions, such as diabetes and hypertension.

In addition to Bulik, Devlin and Kaye, other authors on the two studies include Drs. Silviu-Alin Bacanu, Vibhor A. Sonpar and Weiting Xie, University of Pittsburgh; Kelly L. Klump, Michigan State University; Manfred M. Fichter, University of Munich (Germany) Hospital for Behavioral Medicine; Katherine A. Halmi, New York Presbyterian Hospital; Pamela Keel, University of Iowa; Allan S. Kaplan and D. Blake Woodside, Toronto General Hospital; James E. Mitchell, Neuropsychiatric Institute, Fargo, N.D.; Alessandro Rotondo, University of Pisa, Italy; Michael Strober, University of California at Los Angeles; Janet Treasure, Institute of Psychiatry and South London and Maudsley National Health Service Trust; Andrew Bergen, National Institutes of Health, National Cancer Institute; and Wade H. Berrettini, University of Pennsylvania Center for Neurobiology and Behavior.

For more information about this ongoing international study and its participants, go to “http://www.wpic.pitt.edu/research/angenetics/press.html

These studies were supported by grants from the National Institute of Mental Health, a component of the National Institutes of Health, as well as funds from the Price Foundation of Geneva, Switzerland.

 

UNC School of Medicine contact: Les Lang, (919) 843-9687 UNC Hospitals contact: Stephanie Crayton, (919) 966-2860 or scrayton@unch.unc.edu

For further information please contact Ramona DuBose by email at ramona_dubose@unc.edu