The Genetics Behind Anorexia

The search for an eating disorder treatment, right down to a single gene. Can manipulations of DNA lead to solutions for anorexia?

by Lucy Luong | Preuss School member, staff writer | SQ Vol. 9 (2011-2012)

From television screens, magazines, billboards, movies, and more, the image of a slim figured, flawless skinned, curvaceous female body is present. The picture of the “perfect woman” is seen by the masses everywhere in the media today.

Many women who view these images see them as a message that promotes achieving the seemingly flawless body. However, the ideal figure that many women attempt to attain is nothing more than a highly edited image altered to look faultless and attractive to gain audience attention.

Nonetheless, the message still spreads rapidly to women everywhere as they work to develop a slim figure. The self-consciousness that results from comparing their own bodies to the highly edited ones can lead to various unhealthy physical and mental activities, such as over-exercising, extreme dieting, binge eating, starvation, depression, and high anxiety. These actions and concerns about body imperfections prove to be the initial characteristics of individuals suffering from anorexia nervosa and bulimia nervosa.

Anorexia nervosa and bulimia nervosa are two very serious types of eating disorders. An eating disorder is a complex, psychiatric problem involving irregular eating habits and extreme concern over body weight. People with eating disorders undergo more than just physical problems; they face behaviors that cause them to develop negative attitudes towards their bodies’ appearance and weight. This attitude and behavior are certain symptoms of anorexia and bulimia.

While both are eating disorders, anorexia nervosa and bulimia nervosa have one major difference. Individuals with anorexia tend to refrain from eating while people with bulimia go through a pattern of binge eating or overuse of laxatives in order to lose weight. Anorexia and bulimia are mental health illnesses that have a significantly high mortality rate.

The National Association of Anorexia Nervosa and Associated Disorders gathered mortality statistics on these eating disorders. According to the association, 5 to 10% of eating disorder patients die within ten years, and 18 to 20% die twenty years after identified with the disorder. About 30 to 40% of patients with serious eating disorders are able to have a full recovery. The 2009 American Journal of Psychiatry estimated mortality rates were 4.0% for anorexia nervosa, 3.9% for bulimia nervosa, and 5.2% for other uncategorized eating disorders. The preceding statistics show the evident difficulty of recovering from eating disorders.

Among those who develop an eating disorder, a large proportion remains ill, even if only mentally, throughout life. Recent research done by scientists at University of California, San Diego, School of Medicine and Scripps Translation Science Institute (STSI) has pointed out that genetic variations may be playing a role in influencing one’s recovery from an eating disorder.

Leading the project are Cinnamon Bloss, Ph.D., STSI assistant professor and first author of the study’s paper, Walter H. Kaye, M.D., UCSD’s Eating Disorder Treatment Program director and psychiatry professor, and Nicholas J. Schork, Ph.D., bioinformatics and biostatistics director at STSI and professor at The Scripps Research Institute. From their studies, these researchers discovered certain genetic variations that cause difficulty for individuals to recover from anorexia nervosa or bulimia nervosa. With this new knowledge, further research can be used to create new and effective treatments specific to a patient’s genetic composition and ultimately to treat patients with anorexia nervosa and bulimia nervosa.

Overview of the Study

Bloss explains that the study first began from the stirring questions of why only a small percentage of women spontaneously recover from their eating disorders. Anorexia nervosa and bulimia nervosa are very complicated disorders to treat, and it was hypothesized that a person’s genetic makeup could play a part in answering the question of why a small number of people overcome their eating disorders while many others have a harder time recovering.

“Anorexia and bulimia likely stem from many different causes such as culture, family, life changes, and personality traits,” said Bloss. “But we know biology and genetics are highly relevant in terms of cause and can also play a role in how people respond to treatment. Understanding the genetics behind these conditions is important, because it could eventually help us tailor treatment based on the person’s genetic makeup, with the goal of more personalized and effective treatments.”

The study conducted is the Price Foundation Candidate Gene Project. This project assesses specific genes in a candidate that may play a role in the genetic inability to recover from an eating disorder. The Price Foundation Collaborative Genetic Dataset provided the project with 1878 women to participate in the research study; a total of 1201 women were diagnosed with an eating disorder and 677 women were used as controls.

Researchers at UCSD and STSI were in charge of designing the study. The study consisted of two cohort groups, one group of women over 25 years old and another group of women under 25 years old. The women from each group lived in roughly the same period of time; thus the study made sure outlying factors were taken into consideration.

Both generations consisted of women who either have eating disorders or have recovered from one, allowing for the comparison and location of genes involved in preventing women from recovering. With blood samples taken from the 1878 women studied, the researchers were able to extract DNA samples and measure the genetic variants in the DNAs. Approximately 350 genes were observed, and a total of 5151 single-nucleotide polymorphisms (SNPs) within these genes were analyzed. SNPs are DNA sequences that vary in one single nucleotide (A, T, G, or C) in the sequence. For example, DNA sequences GCAT and GTAT vary in only one single letter; the second single nucleotide is either C or T. These differences result in SNPs.

Along with the genetic makeup of the individual women, observable traits, also known as phenotypes, were examined as well. Hereditary traits such as high anxiety, which can lead to perfectionism, associated with eating disorders were taken into consideration in the research to analyze the role of genetics in these women’s recovery process.

The Role of GABA Genes

The scientists from UCSD and STSI discovered 25 statistically significant SNPs that play a role in the women’s eating disorder recoveries. Ten of the twenty-five SNPs were haplotypes, a mix of alleles inherited together, and located close to each other on a chromosome. They concerned SNPs of GABA genes.

GABA stands for gamma-aminobutyric acid, which is a chemical that controls the central nervous system. A type of neurotransmitter, GABA genes are responsible for many psychological functions and functions regarding the brain. They play a role as a nerve transmitter sending messages to the brain. One of these messages they are responsible for happens to be anxiety or worry, one of the important characteristics that causes eating disorders in individuals.

From the study, GABA genes have shown some amount of responsibility for the outcome of women’s recovery from anorexia, bulimia, or other eating disorders. According to the study, women who did not recover from long-term eatihng disorders displayed higher frequencies of genetic variation in their GABA genes. GABA genes have multiple variations, and various versions can either be detrimental or protective to an individual.

Whether or not these genes will benefit an individual simply depends on heredity and chance. Those who are lucky will receive the protective variation of the GABA gene from their parents that causes them to have less anxiety. However, those who are unlucky will inherit the detrimental variation of the GABA gene that causes them to be more anxious.

Bloss stated, “In terms of our findings, individuals with eating disorders who inherited the unlucky variant were more likely to remain ill with an eating disorder for a longer period of time relative to those with the lucky variant, who were more likely to recover quickly (i.e. before age 25). ”

Although not completely proven, these genes play a responsible role in individual behavior disorders and not just in brain functions. Findings from other research have shown that GABA genes are related to anxiety levels. In this particular study by UCSD and STSI, women with eating disorders who displayed poor recoveries from eating disorders were the most anxious out of all the women in the cohort study. This is because a beneficial variation of the GABA gene is more common in people who recover from their eating disorder.

The research study showed that the control women had distinct SNPs that varied from the women who could not recover from their eating disorders. This distinction substantially supports the hypothesis that genetics does have a crucial role in women’s recovery from anorexia, bulimia, and other eating disorders. In addition, there is an intronic SNP located on chromosome four of the GABRGI gene. This intronic SNP does not produce any proteins and rather strongly connects to chronic eating disorder symptoms. Studies show that there may be genes that will incline an individual to undergo a chronic eating disorder but further research must be done still.

A Call to New Treatment

Through these findings, researchers now have greater insight towards the role of genetics in eating disorders. There are multiple genes that cause eating disorders. Substantial evidence shows that people who develop eating disorder tend to have certain inherited personality trait such as anxiety, from family members who share a common history.

Genes, therefore, do have an infl uence on a person’s susceptibility to recover from an eating disorder. The slightest GABA gene variation can cause a person to inherit greater anxiety and become more vulnerable to eating disorder. With the support of future research, different types of drugs will be developed that target the GABA genes. As the information about the role of genetics in eating disorder recovery becomes more recognizable, treatments of eating disorder will be developed for these individuals’ needs.

WRITTEN BY LUCY LUONG. Lucy Luong is a senior at The Preuss School UCSD. She will graduate from high school in 2012 and attend Dartmouth College next year.


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