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Human Molecular Genetics, 2001, Vol. 10, No. 25 2933-2944
© 2001 Oxford University Press

A genome screen for genes predisposing to bipolar affective disorder detects a new susceptibility locus on 8q

Sven Cichon1,10,+, Johannes Schumacher1, Daniel J. Müller1, Martina Hürter1, Christine Windemuth2, Konstantin Strauch2, Susanne Hemmer1, Thomas G. Schulze3, Gabriele Schmidt-Wolf1,2, Margot Albus4, Margitta Borrmann-Hassenbach4, Ernst Franzek5, Mario Lanczik5, Jürgen Fritze6, Roland Kreiner7, Ulrike Reuner7, Bettina Weigelt7, Jürgen Minges8, Dirk Lichtermann3, Bernhard Lerer9, Kyra Kanyas9, Max P. Baur2, Thomas F. Wienker2, Wolfgang Maier3, Marcella Rietschel3, Peter Propping1 and Markus M. Nöthen10

1Institute of Human Genetics, University of Bonn, Wilhelmstrasse 31, D-53111 Bonn, Germany, 2Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany, 3Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany, 4Mental State Hospital Haar, Vockestrasse 72, D-85540 Haar, Germany, 5Department of Psychiatry, University of Würzburg, Füchsleinstrasse 15, D-97080 Würzburg, Germany, 6Department of Psychiatry, University of Frankfurt, Heinrich-Hoffmann-Strasse 10, D-60528 Frankfurt/Main, Germany, 7Department of Psychiatry, TU Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany, 8Department of Psychiatry, University of Mainz, Untere Zahlbacher Strasse 8, D-55131 Mainz, Germany, 9Department of Psychiatry, Hadassah University, Jerusalem, Israel and 10Department of Medical Genetics, University of Antwerp, Antwerp, Belgium

Bipolar affective disorder (BPAD), also known as manic depressive illness, is a severe psychiatric disorder characterized by episodes of mania and depression. It has a lifetime prevalence of ~1% in all human populations. In order to identify chromosomal regions containing genes that play a role in determining susceptibility to this psychiatric condition, we have conducted a complete genome screen with 382 markers (average marker spacing of 9.3 cM) in a sample of 75 BPAD families which were recruited through an explicit ascertainment scheme. Pedigrees were of German, Israeli and Italian origin, respectively. Parametric and non-parametric linkage analysis was performed. The highest two-point LOD score was obtained on 8q24 (D8S514; LOD score = 3.62), in a region that has not attracted much attention in previous linkage studies of BPAD. The second best finding was seen on 10q25–q26 (D10S217; LOD score = 2.86) and has been reported in independent studies of BPAD. Other regions showing ‘suggestive’ evidence for linkage localized to 1p33–p36, 2q21–q33, 3p14, 3q26–q27, 6q21–q22, 8p21, 13q11 and 14q12–q13. In addition, we aimed at detecting possible susceptibility loci underlying genomic imprinting by analyzing the autosomal genotype data with the recently developed extension of the GENEHUNTER program, GENEHUNTER-IMPRINTING. Putative paternally imprinted loci were identified in chromosomal regions 2p24–p21 and 2q31–q32. Maternally imprinted susceptibility genes may be located on 14q32 and 16q21–q23.

+ To whom correspondence should be addressed at: Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium. Tel: +32 3 820 2491; Fax: +32 3 820 2566; Email: svcichon@uia.ua.ac.be


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