Several population-based twin studies conducted around the world, primarily on individuals with European ancestry, have similarly concluded that AN and BN, as well as related phenotypes such as perfectionism, body dissatisfaction and drive for thinness, are moderately heritable, Bulik indicated.
A series of multisite studies supported by the Price Foundation of Geneva have helped identify possible areas on chromosome 1 for AN and areas on chromosome 10 for BN that may harbor susceptibility loci for these disorders.
Bulik described some of the studies in which she was an investigator, along with many others. Others involved in managing the genetic data were Walter Kaye, M.D., professor of psychiatry at the University of Pittsburgh School of Medicine; Bernie Devlin, Ph.D., associate professor of psychiatry at the University of Pittsburgh School of Medicine; Wade Berrettini, M.D, Ph.D., professor of psychiatry at the University of Pennsylvania School of Medicine; and Andrew Bergen, Ph.D., senior scientist at the Advanced Technology Center of the National Cancer Institute.
"The first study we did involved 192 individuals with anorexia nervosa and their affected relatives," said Bulik. "The probands had anorexia nervosa, but the family members could have had a whole cluster of eating disorder diagnoses. The results were underwhelming. å So we decided to look at what would be the core phenotype for anorexia nervosa to clarify our analysis."
The investigators performed a linkage analysis in a subset (n=37) of families in which at least two affected relatives had diagnoses of restricting AN, a subtype characterized by severe limitation of food intake without the presence of binge-eating or purging behavior. By doing so, the investigators observed that the highest nonparametric linkage (NPL) score was 3.03 at marker D1S3721 on chromosome 1p (Grice et al., 2002).
"Subsequently, we found two genes under that peak--one related to the serotonergic system and one related to opioidergic system that may influence risk for anorexia nervosa," Bulik said.
A second study funded by the Price Foundation looked at bulimia and involved two linkage analyses (Bulik et al., 2003). To identify regions of the genome harboring genetic variants conferring susceptibility to BN, the investigators conducted a linkage analysis of multiplex families with eating disorders who were identified through a proband with BN. Linkage analysis of the entire sample of 308 families yielded a double peak, with the highest nonparametric multipoint maximum LOD score (MLS) of 2.92 on chromosome 10.
The investigators then sought to analyze families who showed noteworthy elevation in vomiting behavior, for which other studies had found a substantial heritability. Consequently, the investigators then performed linkage analysis in a subset of 133 of families in which at least two affected relatives reported a symptom pattern that included self-induced vomiting. The highest MLS score observed (3.39) was on chromosome 10, between markers D10S1430 and D10S1423, thus providing evidence of the presence of a susceptibility locus for BN on chromosome 10p.