Genome wide significant linkage in schizophrenia conditioning on occurrence of depressive episodes.
BACKGROUND
Schizophrenia shows substantial clinical heterogeneity. One common important clinical variable in presentation is the occurrence of episodes of major depression.


METHODS
We undertook analyses in an attempt to detect loci that influence susceptibility to, or modify the clinical expression of, schizophrenia according to the occurrence of episodes of major depression. We used a logistic regression framework in which lifetime presence/absence of major depression was entered as a covariate in the linkage analysis of our UK schizophrenia affected sibling pair series (168 affected sibling pairs typed for a 10 cM map of microsatellite markers).


RESULTS
Inclusion of presence/absence of depression as a covariate detected a genome wide significant linkage signal on chromosome 4q28.3 at 130.7 cM (LOD = 4.59; p = 0.038; increase in maximum LOD over univariate analysis (ILOD) = 3.62). Inclusion of the depression covariate also showed suggestive evidence of linkage on 20q11.21 (LOD = 4.10; expected to occur by chance 0.093 times per genome scan, ILOD = 2.83).


CONCLUSIONS
Our findings identify loci that may harbour genes that play a role in susceptibility to, or modify the risk of, episodes of major depression in people with schizophrenia.
Hamshere
M L
ML
Department of Psychological Medicine, Wales School of Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK.
Williams
N M
NM
Norton
N
N
Williams
H
H
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
O'Donovan
M C
MC
Owen
M J
MJ
Craddock
N
N
D000704:Analysis of Variance; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D003213:Conditioning, Psychological; D003866:Depressive Disorder / Q000235:genetics* / Q000523:psychology; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D007494:Ireland; D019964:Mood Disorders / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D035781:Siblings; D013577:Syndrome; D006113:United Kingdom