PITTSBURGH, March 12 - A multi-center, international collaborative team of researchers is the first to identify a region on chromosome 1 that may contain genes that make an individual vulnerable to developing anorexia nervosa (AN).
The findings add to a growing body of research supporting the belief that genetic transmission - in addition to psychosocial factors - contributes to a person's vulnerability to develop AN.
The study, in the March issue of the American Journal of Human Genetics, is the first genome-wide linkage analysis of eating disorders and uses an affected relative pair research method that looks for genes that run in families where two or more people have a disorder. Results from a linkage study provide stronger evidence of a genetic basis for an illness than those from population-based association studies, where people with a disorder are compared with samples from the general population.
By using a sample of participants from families where at least two relatives had restricting anorexia nervosa (RAN), a clinically defined subtype of AN, researchers identified a possible AN-susceptibility locus on chromosome 1p. Additional regions on chromosomes 2, 4, 5, 8, 9, 16 and 22 also gave genetic linkage signals, though not as statistically strong, indicating there may be several susceptibility genes that underlie the genetic basis for AN.
"The scientific literature has long supported the role of genetics in the etiology of anorexia nervosa. This is the first genetic linkage study to detect specific susceptibility loci for anorexia nervosa and we are excited about the possibility of identifying the particular gene(s) that underlie this linkage signal," said Dorothy Grice, M.D., the study's first author. Dr. Grice is an assistant professor and child psychiatrist at the Center for Neurobiology and Behavior in the department of psychiatry at the University of Pennsylvania School of Medicine.
"It may be that a number of genes contributed to AN and, through additional research, we hope to eventually be able to identify them," said Walter H. Kaye, M.D. professor of psychiatry, University of Pittsburgh School of Medicine and principal investigator for the collaborative study.
Dr. Grice and Wade Berrettini, M.D., Ph.D., director of the Center for Neurobiology and Behavior and professor of psychiatry at Penn's medical school, using blood samples collected by the collaborative study, performed an allele-sharing linkage strategy to identify loci (locations on chromosomes) that may contribute to AN.
Analysis of the initial sample of 192 families with at least one affected relative pair with AN or other related eating disorders - including bulimia nervosa - resulted in only modest evidence for linkage. To increase the ability to detect linkage, the researchers narrowed the linkage analysis to include only those families in which at least two relatives had diagnoses of restricting anorexia nervosa (RAN), a clinically defined subtype of AN characterized by severe limitation of food intake without the presence of binge-eating or purging.
"When we narrowed the sample to relatives who had the same form of AN, the linkage analysis pointed to marker D1S3721 on chromosome 1p, and additional genotyping provided evidence for the AN-susceptibility gene on chromosome 1p," said Dr. Berrettini.
Currently, these collaborative researchers are looking for people with restricting-type AN who also have two parents who are willing to participate in research studies to identify genetic bases for eating disorders. Please see http://www.anbn.org for more information. All information is kept strictly confidential.
Other authors include: K.A. Halmi, department of psychiatry, Cornell University, White Plains, N.Y.; M.M. Fichter, Klinik Roseneck, Hospital for Behavioral Medicine, University of Munich, Prien, Germany; M. Strober, department of psychiatry and biobehavioral sciences Neuropsychiatric Institute, University of California, Los Angeles; D.B. Woodside and A.S. Kaplan, The Toronto Hospital, department of psychiatry, University of Toronto; J.T. Treasure, Institute of Psychiatry, Kings College, London; P.J. Magistretti, Institute of Physiology, University of Lausanne, Lausanne, Switzerland; and C.M. Bulik, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Va.
Craig Dunhoff, University of Pittsburgh Medical Center
Ellen O'Brien, University of Pennsylvania School of Medicine