Suggestive Evidence of a Locus on Chromosome 10p Using the NIMH Genetics Initiative Bipolar Affective Disorder Pedigrees Tatiana Foroud, 1 * Peter F. Castelluccio, 1 Daniel L. Koller, 1 Howard J. Edenberg, 1 Marvin Miller, 1 Elizabeth Bowman, 1 N. Leela Rau, 1 Carrie Smiley, 1 John P. Rice, 2 Alison Goate, 2 Christopher Armstrong, 2 Laura J. Bierut, 2 Theodore Reich, 2 Sevilla D. Detera-Wadleigh, 3 Lynn R. Goldin, 3b Judith A. Badner, 3a Juliet J. Guroff, 3 Elliot S. Gershon, 3a Francis J. McMahon, 4a Sylvia Simpson, 4 Dean MacKinnon, 4 Melvin McInnis, 4 O. Colin Stine, 4c J. Raymond DePaulo, 4 Mary C. Blehar, 5 and John I. Nurnberger, Jr., 6 1 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 2 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 3 Clinical Neurogenetics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 4 Department of Psychiatry, Johns Hopkins University Medical School, Baltimore, Maryland 5 Mood, Anxiety, and Personality Disorders Research Branch, National Institute of Mental Health, National Institutes of Health, Rockville, Maryland 6 Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana As part of a four-center NIMH Genetics Ini- tiative on Bipolar Disorder, a genome screen using 365 markers was performed on 540 DNAs from 97 families, enriched for af- fected relative pairs. This is the largest uni- formly ascertained and assessed linkage sample for this disease, and includes 232 subjects diagnosed with bipolar I (BPI), 32 with schizo-affective, bipolar type (SABP), 72 with bipolar II (BPII), and 88 with unipo- lar recurrent depression (UPR). A hierar- chical set of definitions of affected status was examined. Under Model I, affected indi- viduals were those with a diagnosis of BPI or SABP, Model II included as affected those fitting Model I plus BPII, and Model III in- cluded those fitting Model II plus UPR. This data set was previously analyzed using pri- marily affected sib pair methods. We report the results of nonparametric linkage analy- ses of the extended pedigree structure using the program Genehunter Plus. The strong- est finding was a lod score of 2.5 obtained on chromosome 10 near the marker D10S1423 with diagnosis as defined under Model II. This region has been previously implicated in genome-wide studies of schizophrenia and bipolar disorder. Other chromosomal regions with lod scores over 1.50 for at least one Model Included chromosomes 8 (Model III), 16 (Model III), and 20 (Model I). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:18– 23, 2000 © 2000 Wiley-Liss, Inc. KEY WORDS: bipolar affective disorder; ge- netics; linkage; nonparamet- ric analysis; genomic survey INTRODUCTION Bipolar affective disorder (BP) is a disabling condi- tion involving dysregulation of multiple physiologic functions, including mood, appetite, sleep, and activity [Goodwin and Jamison, 1990]. It occurs in about 1% of the population, usually with onset in early adulthood. BP has been observed to aggregate within families [Nurnberger et al., 1994b], with evidence from twin and adoption studies suggesting a significant genetic con- tribution to risk [Bertelsen et al., 1977; Mendlewicz Contract grant sponsor: NIMH; Contract grant numbers: U01 MH46282, U01 MH54794, U01 MH46280, U01 MH54723, U01 MH46274, and U01 MH54701. a Present address: Department of Psychiatry, Biological Sci- ences Division, University of Chicago, Chicago, IL. b Present address: Genetic Epidemiology Branch, DCEG, NCI, Bethesda, MD. c Present address: Center for the Genetics of Asthma and Com- plex Diseases, School of Medicine, University of Maryland, Bal- timore, MD. *Correspondence to: Tatiana Foroud, Ph.D., Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 W. Walnut Street IB-155, Indianapolis, IN 46202. E-mail: tforoud@iupui.edu Received 30 July 1999; Accepted 26 August 1999 American Journal of Medical Genetics (Neuropsychiatric Genetics) 96:18–23 (2000) © 2000 Wiley-Liss, Inc.