Evidence for Linkage by Transmission Disequilibrium Test Analysis of a Chromosome 22 Microsatellite Marker D22S278 and Bipolar Disorder in a Palestinian Arab Population Mustafa Mujaheed, 1 Marilys Corbex, 2 Pesach Lichtenberg, 3 Douglas F. Levinson, 4 Jean-Francois Deleuze, 5 Jacques Mallet, 2 and Richard P. Ebstein 3 * 1 Palestinian Research Center for Genetics of Mental Disorders, Bethlehem, Palestine 2 Laboratoire de Genetique Moleculaire de la Neurotransmission et des Processus Neurodegeneratifs (L.G.N.), Centre National de la Recherche Scientifique (CNRS), Paris, France 3 S. Herzog Memorial Hospital, Jerusalem, Israel 4 Department of Psychiatry and Center for Neurobiology and Behavior, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 5 Aventis, Iury, France A number of linkage studies suggest a schizophrenia susceptibility locus on chro- mosome 22, particularly with microsatellite marker D22S278 (22q12). In addition to some evidence for linkage to schizophrenia in this region, linkage to bipolar disorder using this marker has also been reported. We tested a group of 60 Bipolar I triads and an expanded group of 79 Bipolar I and Bipo- lar II triads recruited from a Palestinian Arab population for linkage with the D22S278 marker. Significant linkage was observed using the extended transmission disequilibrium test for multiallelic markers (ETDT) for both Bipolar I (P = 0.031) and the expanded group of Bipolar I and Bipolar II (P = 0.041). These weakly positive results are at least consistent with the hypothesis that this region of chromosome 22 might harbor a susceptibility locus for both major psycho- ses and should be considered for more in- tensive study. Am. J. Med. Genet. (Neuropsy- chiatr. Genet.) 96:836–838, 2000. © 2000 Wiley-Liss, Inc. KEY WORDS: bipolar disorder; schizophre- nia; transmission disequilib- rium test; ETDT; chromosome 22; D22S278; Palestinian Arab INTRODUCTION In addition to a reported linkage to schizophrenia on chromosome 22 [Coon et al., 1994; Pulver et al., 1994], bipolar disorder has also been linked to markers on this chromosome [Edenberg et al., 1997; Lachman et al., 1997; Liang et al., 1999; Saito et al., 1999; Schwab and Wildenauer, 1999]. Two areas on chromosome 22 pre- viously identified with schizophrenia are of interest for bipolar disorder. The first is near the microdeletion as- sociated with velocardiofacial syndrome (VCFS) at 22q11 and spanning 13 cM [Lachman et al., 1997]. A second area of interest is at 22q12-13, where linkage disequilibrium was observed between disease and mi- crosatellite marker D22S278 [Liang et al., 1999] in 28 triads. In the current study, we examined microsatel- lite marker D22S278 for linkage to bipolar disorder using the transmission disequilibrium test (TDT) and its extension for multiallelic markers [Sham and Cur- tis, 1995] in a group of bipolar triads (proband and both parents) recruited from a culturally and ethnically akin Palestinian Arab population not previously stud- ied for either linkage or association with the major psy- choses. MATERIALS AND METHODS Clinical Sample There were 79 triads, including 52 males and 27 fe- male bipolar patients. Sixty probands were diagnosed as Bipolar (BP) I and 19 probands as BP II. Ten fami- lies comprised only one BP II-affected proband. All pa- tients were interviewed by an experienced psychiatrist (MM) using the SCID interview. Diagnosis of bipolar disorder was assigned on the basis of the interview and medical records according to DSMIV criteria [APA, 1994]. Thirteen families had more than one affected sib and a total of 30 probands were related. Contract grant sponsor: NIMH; Contract grant number: KO2- 01207; Contract grant sponsor: Aventis. *Correspondence to: Prof. Richard P. Ebstein, Research Labo- ratory, S. Herzog Memorial Hospital, P.O. Box 35300, Jerusalem 91351, Israel. E-mail: ebstein@netmedia.net.il Received 28 February 2000; Accepted 1 June 2000 American Journal of Medical Genetics (Neuropsychiatric Genetics) 96:836–838 (2000) © 2000 Wiley-Liss, Inc.