G72 and its association with major depression and neuroticism in large population-based groups from Germany.
OBJECTIVE
G72 is among the most frequently replicated vulnerability genes for schizophrenia and bipolar disorder. The authors previously found identical haplotypes of markers M23 and M24 to be associated with schizophrenia, bipolar disorder, and panic disorder. Given both the well-recognized familial clustering across these disorders and recent linkage findings implicating the region harboring G72 in the etiology of major depression and panic disorder, we can hypothesize that G72 should also be involved in the etiology of major depression. Neuroticism, measuring trait anxiety, may be the endophenotypic link underlying genetic associations with G72 across diagnostic boundaries. The authors tested whether the previously observed risk haplotypes are also associated with major depression and neuroticism.


METHODS
The authors performed a standard haplotype analysis in a group of 500 major depression patients and 1,030 population-based comparison subjects. The authors also performed an exploratory analysis on 10 additional G72 markers using a novel haplotype-sharing approach. They performed a quantitative trait haplotype analysis in an independent group of 907 individuals phenotyped for neuroticism.


RESULTS
The previously identified M23-M24 risk haplotype was significantly associated with major depression and high levels of neuroticism. The haplotype-sharing analysis also implicated the same region, whereas more proximal markers showed no association with major depression.


CONCLUSIONS
This is the first study to the authors' knowledge to implicate the G72 locus in the etiology of major depression and neuroticism. The results strengthen the notion of a genetic overlap between diagnoses, commonly conceptualized as distinct entities. Neuroticism may constitute the common underlying endophenotypic link.
Rietschel
Marcella
M
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Beckmann
Lars
L
Strohmaier
Jana
J
Georgi
Alexander
A
Karpushova
Anna
A
Schirmbeck
Frederike
F
Boesshenz
Katja V
KV
Schmäl
Christine
C
Bürger
Christin
C
Jamra
Rami Abou
RA
Schumacher
Johannes
J
Höfels
Susanne
S
Kumsta
Robert
R
Entringer
Sonja
S
Krug
Axel
A
Markov
Valentin
V
Maier
Wolfgang
W
Propping
Peter
P
Wüst
Stefan
S
Kircher
Tilo
T
Nöthen
Markus M
MM
Cichon
Sven
S
Schulze
Thomas G
TG
D000328:Adult; D001008:Anxiety Disorders / Q000453:epidemiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005828:Genetics, Population; D005858:Germany; D006239:Haplotypes; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009497:Neurotic Disorders / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype
D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins