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Is there a genetic risk for anorexia?

 

Lee Wheeler-Berliner

 

Question

Is there a genetic factor in the development of anorexia nervosa that affects the risk factors of relatives of probands?

Relevant Studies

Many studies have been conducted on the genetics of anorexia nervosa and bulimia nervosa since the 1970s. Interest in genetics has increased in the recent years with new technologies and methods for studying genes and their effects on various phenotypes. Anorexia nervosa is labeled as a phenotype by psychologists studying its heritability. Research has consisted primarily of twin studies but a push to discover specific genes has led to various types of research, including connections with certain conditions in animals and anorexia nervosa. A 1997 study by Treasure and Owen compared the commonalities of anorexia in humans and thin sow syndrome in pigs. Their review of the current literature also looked at body composition, which was seen to be highly heritable in animals. Certain chemicals were used in treatment and 5HT was found to effectively treat "pig anorexia", suggesting possibilities for human treatment (Treasure & Owen, 1997).

Much of the research done since 1997 has reported high rates of heritability for anorexia, though there is some dissent as to the actual truth. Two studies took a large sample of twins and used surveys to determine heritability. Kortegaard et al., published a report in Psychological Medicine in 2001 based on a survey of over 30,000 twins. A questionnaire was mailed to participants, whose names were taken from the Danish twin database, that consisted of three simple questions. The first question was concerned with self-assessment of anorexia and simply asked, "Have you ever had anorexia nervosa?" The second question focused on others opinions and asked if any family or friends had ever suggested that you had been anorexic. The third question asked about bulimia, which will not be discussed in this review. After the surveys were returned, 190 MZ pairs and 248 DZ pairs were available for analysis (all pairs were females). The resulting heritability ratio for anorexia nervosa was found to be 0.48-0.52 (Kortegaard et al., 2001).

This estimated ratio is consistent with what is commonly called the Virginia Twin Study performed by Wade et al., in 2000. As reported in the American Journal of Psychiatry, 2,163 female twins were studied via phone interviews and face to face interviews. The sample contained 597 MZ twins and 433 DZ twins who were evaluated using a very broad definition of anorexia. Judgements were based on criteria from the DSM-III-R using first the strict criteria, then excluding amenorrhea as a symptom, and thirdly by excluding feelings of fatness even when emaciated. While the researchers state they could not completely eliminate environmental factors, they claim a heritability rate of 0.58 for anorexia nervosa (Wade et al., 2000).

The consistency between these two studies is a step forward for proponents of heritability. In 1999, Fairburn et al., published a review in the International Journal of Eating Disorders that concludes that the heritability of eating disorders is still unknown. The major complaint of previous studies is that they are inconsistent, giving heritability ranges of between 0% and 70%. Also, small sample sizes and violation of the Equal Environments Assumption are cited as reasons for discrediting the claims made by Kendler in Virginia and Holland and Treasure in the UK, which Fairburn points to as the two leading studies at that time (Fairburn et al., 1999).

New research is being done to pinpoint particular sequences on the genome that relate to anorexia. Campbell et al., has examined alleles of markers and one in particular, allele 13 of D11S911 has been shown to be over represented in anorexia patients and could therefore be part of the genetic sequencing of anorexia. (Campbell et al., 1999). The suggestion that a mutation could be related to the onset of the condition opens the door for much research with the genome.

 

Methodologies

Just as Fairburn pointed out in 1999, there are flaws within the twin studies that limit their validity. Even the newer studies fail to mention the Equal Environments Assumption and they each have specific flaws. Kortegaardís research is based entirely on self-assessment and self-report. It is plausible that a participant with no knowledge of actual criteria for anorexia stated that she did have it on the questionnaire. There was no clinical assessment of the persons in the study. Is it possible that varying degrees of anorexia (i.e. a mild condition where help is not immediately sought versus a hospitalized patient) result in varying degrees of heritability? The notion of varying levels of condition affecting heritability also remains hidden in Wadeís research. By watering down the criteria for the disease there is the possibility that more significant findings are going unnoticed for the sake of returning an overall heritability rating. While measures were taken to avoid a bias, these studies appear to stretch the results to show a significant level of heritability.

In part, provisions were made by researchers and the results appear as they do because of the difficulty in studying this condition. Eating disorders appear in roughly 7.2% of women and 1.2% of males (Kortegaard et al., 2001) and the occurrence of twins, either monozygotic or dizygotic, is also small. It is therefore difficult to find research participants who fit both categories.

 

Conclusions

At the present time, a majority of researchers report that anorexia nervosa is heritable with a rate of anywhere from 0% to 80%, though the most recent indications point towards a 0.48-0.58 range. Enough evidence has been found that further studies are examining specific gene sequences to look for mutations that may "cause" anorexia.

 

Current Significance

What does this mean to a person with anorexia nervosa? Or perhaps more importantly what does it mean to their relatives? There is not a significant amount of discussion as to what gain is sought by researching heritability. On the one hand, it has progressed from phenotype research into genotype research, which could result in new ways of preventing anorexia nervosa in the womb or discovering new medications to help treat it. However, stating to a patient that the condition they suffer from has a heritability of 0.58 does not appear to have any significant value.

Additionally, there is no discussion as to what specifically generates the remaining causes of anorexia. Where does the other 0.42 come from? Research on heritability cannot be used to its fullest extent by the general public without an understanding of the interactions and correlations between a personís environment and their genes. Without this data, a person is left to wonder if they really are more susceptible to anorexia just because their twin sister had it. A relevant meaning of the statement, "Anorexia nervosa has a heritability of 0.58" does not have much meaning for people outside of the field of research.

 

Future Research

There are diseases that have a genetic basis yet their appearance is largely determined by the surrounding environment. Some genes are only expressed if a person eats too much or too little of a particular food. The emotional components of anorexia seem to be highly specific to a personís situation and what environmental factors are leading to their obsessions with weight and feelings of fatness. When such causes are known, then a researcher, or even a parent, can determine the degree of risk that their patient or child faces. If risk is known, then preventive methods can be taken early on.

Is it plausible to state that a person is "at risk" for developing anorexia nervosa? Further research should look into this question by studying the correlations between environmental factors and genetic factors that result in anorexia. Also, the studies have used only female twin pairs, mostly due to a lack of subjects of male twin pairs and mixed sex pairs that had anorexia nervosa. The differences in heritability across twin brothers or between brothers and sisters are not known. If an older sister has anorexia, does it effect the likelihood of a younger brother developing the condition? Does that effect differ for a younger sister?

Current research has also focused only on siblings and family members of the same generation. If there is a specific gene for anorexia nervosa, is it passed on from generation to generation, suppressed in some people and expressed in others, in the same manner has a gene for baldness or blue eyes? Since the investigation into genetics began mainly in the 1970ís, there has not yet been sufficient time to study the offspring of many anorexia sufferers. Using the Virginia or Danish Twin Registries, the rate of anorexia nervosa in offspring could be compared and used to examine the extent that it is passed on between generations like other traits.

When these questions are answered, then a sufficient analysis of risk factors can be studied that will have much practical use for the general public. Mothers who had anorexia themselves will know that their offspring may be susceptible to the condition at higher rates than other children, and can therefore attempt to manipulate the environment to prevent onset. Likewise if one child in the family suffers, the exact implications for brothers and sisters will be known. These findings could also open the doors for new methods of family therapy in the treatment of anorexia nervosa.

 

Results

Is there a genetic component in the development of anorexia nervosa? The current findings say yes. Is it inherited? That question remains unanswered. Until it is, then the presence or absence of risk factors for developing anorexia nervosa cannot be discovered.

 

References

Campbell, DA., Sundaramurthy, D., Gordon, D., Markham, AF., Pieri, LF. (1999)

Fairburn, C., Cowen, P., Harrison, P. (1999) Twin studies and the etiology of eating

disorders. International Journal of Eating Disorders, Vol. 26, 349-358.

http://www3.interscience.wiley.com/cgi-bin/jtoc?ID=34698

Kipman, A., Gorwood, P., Mouren-Simeoni, M., Ades, J. (1999) Genetic factors in

http://www.sciencedirect.com/science/journal/09249338

Kortegaard, L., Hoerder, K., Joergensen, J., Gillberg, C., Kyvik, K. (2001) A preliminary

http://gateway1.ovid.com/

Treasure, J., Owen, J. (1997) Intriguing links between animal behavior and anorexia

nervosa. International Journal of Eating Disorders, Vol. 21 (4), 307-311.

http://www3.interscience.wiley.com/cgi-bin/jtoc?ID=34698

Wade, T., Bulik, C., Neale, M., Kendler, K. (2000) Anorexia nervosa and major

http://gateway1.ovid.com/

 

 

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