Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21.
Schizophrenia is a common disorder characterized by psychotic symptoms; diagnostic criteria have been established. Family, twin and adoption studies suggest that both genetic and environmental factors influence susceptibility (heritability is approximately 71%; ref. 2), however, little is known about the aetiology of schizophrenia. Clinical and family studies suggest aetiological heterogeneity. Previously, we reported that regions on chromosomes 22, 3 and 8 may be associated with susceptibility to schizophrenia, and collaborations provided some support for regions on chromosomes 8 and 22 (refs 9-13). We present here a genome-wide scan for schizophrenia susceptibility loci (SSL) using 452 microsatellite markers on 54 multiplex pedigrees. Non-parametric linkage (NPL) analysis provided significant evidence for an SSL on chromosome 13q32 (NPL score=4.18; P=0.00002), and suggestive evidence for another SSL on chromosome 8p21-22 (NPL=3.64; P=0.0001). Parametric linkage analysis provided additional support for these SSL. Linkage evidence at chromosome 8 is weaker than that at chromosome 13, so it is more probable that chromosome 8 may be a false positive linkage. Additional putative SSL were noted on chromosomes 14q13 (NPL=2.57; P=0.005), 7q11 (NPL=2.50, P=0.007) and 22q11 (NPL=2.42, P=0.009). Verification of suggestive SSL on chromosomes 13q and 8p was attempted in a follow-up sample of 51 multiplex pedigrees. This analysis confirmed the SSL in 13q14-q33 (NPL=2.36, P=0.007) and supported the SSL in 8p22-p21 (NPL=1.95, P=0.023).
Blouin
J L
JL
Division of Medical Genetics, University of Geneva Medical School and Cantonal Hospital, Switzerland.
Dombroski
B A
BA
Nath
S K
SK
Lasseter
V K
VK
Wolyniec
P S
PS
Nestadt
G
G
Thornquist
M
M
Ullrich
G
G
McGrath
J
J
Kasch
L
L
Lamacz
M
M
Thomas
M G
MG
Gehrig
C
C
Radhakrishna
U
U
Snyder
S E
SE
Balk
K G
KG
Neufeld
K
K
Swartz
K L
KL
DeMarchi
N
N
Papadimitriou
G N
GN
Dikeos
D G
DG
Stefanis
C N
CN
Chakravarti
A
A
Childs
B
B
Housman
D E
DE
Kazazian
H H
HH
Antonarakis
S
S
Pulver
A E
AE
D000328:Adult; D002882:Chromosomes, Human, Pair 13; D002898:Chromosomes, Human, Pair 8; D004198:Disease Susceptibility; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D008957:Models, Genetic; D012559:Schizophrenia / Q000235:genetics*