ORIGINAL ARTICLES A Search for Susceptibility Loci for Anorexia Nervosa: Methods and Sample Description Walter H. Kaye, Lisa R. Lilenfeld, Wade H. Berrettini, Michael Strober, Bernie Devlin, Kelly L. Klump, David Goldman, Cynthia M. Bulik, Katherine A. Halmi, Manfred M. Fichter, Allan Kaplan, D. Blake Woodside, Janet Treasure, Katherine H. Plotnicov, Christine Pollice, Radhika Rao, and Claire W. McConaha Background: Eating disorders have not traditionally been viewed as heritable illnesses; however, recent family and twin studies lend credence to the potential role of genetic transmission. The Price Foundation funded an international, multisite study to identify genetic factors contributing to the pathogenesis of anorexia nervosa (AN) by recruiting affective relative pairs. This article is an overview of study methods and the clinical characteristics of the sample. Methods: All probands met modified DSM-IV criteria for AN; all affected first, second, and third degree relatives met DSM-IV criteria for AN, bulimia nervosa (BN), or eating disorder not otherwise specified (NOS). Probands and affected relatives were assessed diagnostically with the Structured Interview for Anorexia and Bulimia. DNA was collected from probands, affected relatives and a subset of their biological parents. Results: Assessments were obtained from 196 probands and 237 affected relatives, over 98% of whom are of Caucasian ancestry. Overall, there were 229 relative pairs who were informative for linkage analysis. Of the pro- band-relative pairs, 63% were AN-AN, 20% were AN-BN, and 16% were AN-NOS. For family-based association analyses, DNA has been collected from both biological parents of 159 eating-disordered subjects. Few significant differences in demographic characteristics were found between proband and relative groups. Conclusions: The present study represents the first large- scale molecular genetic investigation of AN. Our success- ful recruitment of over 500 subjects, consisting of affected probands, affected relatives, and their biological parents, will provide the basis to investigate genetic transmission of eating disorders via a genome scan and assessment of candidate genes. Biol Psychiatry 2000;47:794 – 803 © 2000 Society of Biological Psychiatry Key Words: Anorexia nervosa, bulimia nervosa, eating disorders, genetics, linkage analysis, affected relative pairs Introduction A norexia nervosa (AN) is characterized by an obses- sively morbid dread of body fat that drives, then sustains, an unrelenting avoidance of normal body weight (American Psychiatric Association 1994). It is widely assumed to have a complex, multifactorial etiology, yet psychological theories of pathogenesis have largely pre- vailed in explanatory paradigms put forward in recent decades. Likewise, social influences have been implicated in its causation in the light of mainstream cultural attitudes in industrialized countries favoring thinness as a beauty ideal. Although a role for causal psychosocial factors is not in question, certain well-established observations regarding AN presentation argue persuasively for its qualitative distinction from mere extreme dieting, and against an etiological focus on nonbiological determinants alone in accounting for its development, progression, and morbid- ity. For example, weight-loss efforts in the general female population are frequent, yet AN is hardly a common illness—its lifetime prevalence among females is esti- mated to be 0.1%– 0.7% (Hoek 1998). Second, in the majority of acutely ill patients, dietary restriction is highly entrenched, and resistance to initial therapeutic interven- tion is reflected in an unusually protracted time to achieve full remission of illness (Strober et al 1997). Third, AN appears to covary with other psychopathological risk From The Price Foundation Collaborative Group: Eating Disorders Module, Western Psychiatric Institute & Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (WHK, BD, KLK, KHP, CP, RR, CWM); Department of Psychology, Georgia State University, Atlanta (LRL); Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia (WHB); Neuropsychiatric Institute and Hospital, School of Medicine, University of California at Los Angeles, Los Angeles (MS); National Institute on Alcohol Abuse and Alco- holism (NIAAA), National Institutes of Health (NIH), Bethesda, Maryland (DG); Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond (CMB); New York Presbyterian Hospital-Westchester, Weill Medical College of Cornell University, White Plains, New York (KAH); Klinik Roseneck, Hospital for Behavioral Medicine, Munich, Germany (MMF); Department of Psychiatry, The Toronto Hospital, Toronto, Canada (AK, DBW); and the Institute of Psychiatry, Maudsley and Bethlem Royal Hospital, London, England (JT). Address reprint requests to Walter H. Kaye, M.D., Western Psychiatric Institute and Clinic, 3811 O’Hara Street E-724, Pittsburgh PA 15213. Received December 14, 1998; revised May 5, 1999; revised August 16, 1999; accepted August 30, 1999. © 2000 Society of Biological Psychiatry 0006-3223/00/$20.00 PII S0006-3223(99)00240-1