A systematic genomewide linkage study in 353 sib pairs with schizophrenia.
We undertook a genomewide linkage study in a total of 353 affected sib pairs (ASPs) with schizophrenia. Our sample consisted of 179 ASPs from the United Kingdom, 134 from Sweden, and 40 from the United States. We typed 372 microsatellite markers at approximately 10-cM intervals. Our strongest finding was a LOD score of 3.87 on chromosome 10q25.3-q26.3, with positive results being contributed by all three samples and a LOD-1 interval of 15 cM. This finding achieved genomewide significance (P<.05), on the basis of simulation studies. We also found two regions, 17p11.2-q25.1 (maximum LOD score [MLS] = 3.35) and 22q11 (MLS = 2.29), in which the evidence for linkage was highly suggestive. Linkage to all of these regions has been supported by other studies. Moreover, we found strong evidence for linkage (genomewide P<.02) to 17p11.2-q25.1 in a single pedigree with schizophrenia. In our view, the evidence is now sufficiently compelling to undertake detailed mapping studies of these three regions.
Williams
N M
NM
Neuropsychiatric Genetics Unit, Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, United Kingdom.
Norton
N
N
Williams
H
H
Ekholm
B
B
Hamshere
M L
ML
Lindblom
Y
Y
Chowdari
K V
KV
Cardno
A G
AG
Zammit
S
S
Jones
L A
LA
Murphy
K C
KC
Sanders
R D
RD
McCarthy
G
G
Gray
M Y
MY
Jones
G
G
Holmans
P
P
Nimgaonkar
V
V
Adolfson
R
R
Osby
U
U
Terenius
L
L
Sedvall
G
G
O'Donovan
M C
MC
Owen
M J
MJ
D008040:Genetic Linkage / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D012559:Schizophrenia / Q000235:genetics*; D035781:Siblings; D013548:Sweden; D006113:United Kingdom; D014481:United States