Craig Johnson, PhD and Cindy Bulik, PhD

The recent completion of the Human Genome Project has drawn widespread attention to the rapidly accelerating field of genetic research. Interestingly, significant genetic work has been occurring in the eating disorders field that has not been sufficiently shared with the public. One of the largest contributions in this area of research comes from a collaborative group of investigators under the leadership of Principal Investigator Walter Kaye, M.D. The Collaborative Group includes several international research sites (listed under Investigation: Site Investigators), that have been conducting state-of-the-art genetic research related to eating disorders over the last five years.

Relative Risk

The exploration of possible genetic factors contributing to eating disorders is well founded. It has been observed for decades that eating disorders sometimes run in families. Even when relatives of a woman with an eating disorder have not been clinically diagnosed as suffering from an eating disorder, many clinicians often hear tales from patients about relatives displaying traits associated with eating disorders. Clients may recall mothers, aunts, or fathers who were "obsessed with weight," "ate like a bird," or "hated their appearance."

Formal family studies have shown that relatives of individuals with eating disorders are at substantially greater risk for developing eating disorders themselves. This is commonly referred to as significantly elevated relative risk. In fact, preliminary studies indicate individuals with a mother or sister who has suffered from anorexia are twelve times more likely than people, without a family history, to develop anorexia. In addition, these same family members have a four times greater risk for developing bulimia. These relative risk levels reveal the substantial familial influences with regard to eating disorders.

In spite of a general awareness that family influences impact eating disorders sufferers, clinical observation and family studies have yet to determine why eating disorders run in families. An understanding that family members model disordered eating behaviors and attitudes would suggest environmental transmission. In addition, or perhaps alternatively, the transmission could also be due to genetics. Recent twin studies have shed some light on this nature vs. nurture debate.

Twin Studies

The study of twins offers the unique opportunity to examine the extent to which the transmission of a disorder in families is due to environmental or genetic factors. Identical twins share all of their genes and fraternal twins share, on average, half of their genes. If a disorder occurs in both members of identical twin pairs more often than it occurs in both members of fraternal twin pairs, then the disorder can be said to be influenced by genes.

In the study of genetic influence, the term shared environment refers to those aspects of environment that are shared by both members of a twin pair such as socioeconomic status, religion, and general parenting style. The term unique environment, in contrast, refers to those environmental influences that are experienced by only one member of a twin pair (e.g., trauma, participating in sports that emphasize thinness). Several population-based twin studies have been conducted in Virginia, Australia and Minnesota and have addressed the genetic and environmental factors which contribute to the development of anorexia and bulimia. These studies have also examined genetic and environmental influences on related traits such as drive for thinness and body dissatisfaction. The results have been surprisingly consistent in showing a substantial genetic contribution to anorexia nervosa and bulimia nervosa as well as to the traits that are associated with these disorders. When the environmental influences are considered together, the unique environmental effects have more significance than the shared environmental effects.

Single Genes vs. Multiple Genes?

Although these initial studies offer strong support for the notion that genes contribute to the development of eating disorders, the specific inheritance patterns are still unclear. Like other behavioral disorders, anorexia and bulimia nervosa are complex disorders. This means that these disorders are likely to be caused by multiple genes and environmental factors with varied effects, unlike monogenic diseases (caused by one gene) such as Huntington's disease.

Obesity is a complex trait that has been studied extensively from a genetic perspective. There have been several single-gene mutations identified that lead to rare forms of obesity. However, taken together, these single-gene mutations only account for a small percentage of obesity cases. Future research dedicated to examining the risk for obesity will no doubt lead to the understanding of multiple genes and environmental variables that may influence obesity such as sedentary lifestyle, high fat diets, and overeating.

It is theoretically possible that single-gene mutations might exist which result in anorexia, bulimia, or other disordered eating (e.g., a mutation that affects the functioning of the hypothalamus, which plays a major role in hunger and satiety). However, it is more likely that, as with obesity, there will be multiple genes interacting with environmental variables.

For anorexia nervosa, the high-risk genes might be for traits such as perfectionism, orderliness, low tolerance for new situations, maturity fears, low self-esteem and overall anxiety. However, even if an individual was at high genetic risk (i.e., possessed several of these relevant genes), she might never develop anorexia nervosa if she did not live in a culture such as ours which emphasizes dieting and thinness. Researchers are also beginning to understand how dieting, exercise, semi-starvation, and amennorhea may actually be used to avoid or inappropriately cope with developmental demands of adolescence and young adulthood.

The Future

Although the above considerations are presented as speculation, it is clear that a better understanding of the genetic contribution to eating disorders might inform and improve both prevention and treatment efforts. If genes that play a causal role in eating disorders can be identified, we will then be able to identify at-risk individuals with greater precision. Once relevant genes are identified, researchers and health professionals will be able to identify high-risk individuals by their genotypes. Currently, the best method for identifying high-risk individuals is the consideration of family history as well as environmental factors such as peer influence, participation in high-risk sports or activities, dieting behaviors, etc. Given that widespread prevention efforts have not eliminated eating disorders altogether, more targeted prevention directed towards those who are genetically vulnerable could be more effective and definitely more efficient.

Ultimately, and much further in the future, one could conceive of gene therapy to decrease or eliminate genetic risk in genetically vulnerable individuals. Without a doubt, rapidly developing knowledge in this area offers the promise of new solutions to these devastating illnesses.