A genome screen for genes predisposing to bipolar affective disorder detects a new susceptibility locus on 8q.
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 approximately 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.
Cichon
S
S
Institute of Human Genetics, University of Bonn, Wilhelmstrasse 31, D-53111 Bonn, Germany. svcichon@uia.ua.ac.be
Schumacher
J
J
Müller
D J
DJ
Hürter
M
M
Windemuth
C
C
Strauch
K
K
Hemmer
S
S
Schulze
T G
TG
Schmidt-Wolf
G
G
Albus
M
M
Borrmann-Hassenbach
M
M
Franzek
E
E
Lanczik
M
M
Fritze
J
J
Kreiner
R
R
Reuner
U
U
Weigelt
B
B
Minges
J
J
Lichtermann
D
D
Lerer
B
B
Kanyas
K
K
Baur
M P
MP
Wienker
T F
TF
Maier
W
W
Rietschel
M
M
Propping
P
P
Nöthen
M M
MM
D001714:Bipolar Disorder / Q000235:genetics*; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009679:Nuclear Family; D010375:Pedigree; D010641:Phenotype; D014680:Veins / Q000502:physiology
D004247:DNA