title: G72 and its association with major depression and neuroticism in large population-based groups from Germany.
abstract: 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.
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Lars
authors.initials: L
authors.lastname: Beckmann
authors.forename: Jana
authors.initials: J
authors.lastname: Strohmaier
authors.forename: Alexander
authors.initials: A
authors.lastname: Georgi
authors.forename: Anna
authors.initials: A
authors.lastname: Karpushova
authors.forename: Frederike
authors.initials: F
authors.lastname: Schirmbeck
authors.forename: Katja V
authors.initials: KV
authors.lastname: Boesshenz
authors.forename: Christine
authors.initials: C
authors.lastname: Schmäl
authors.forename: Christin
authors.initials: C
authors.lastname: Bürger
authors.forename: Rami Abou
authors.initials: RA
authors.lastname: Jamra
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
authors.forename: Susanne
authors.initials: S
authors.lastname: Höfels
authors.forename: Robert
authors.initials: R
authors.lastname: Kumsta
authors.forename: Sonja
authors.initials: S
authors.lastname: Entringer
authors.forename: Axel
authors.initials: A
authors.lastname: Krug
authors.forename: Valentin
authors.initials: V
authors.lastname: Markov
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Stefan
authors.initials: S
authors.lastname: Wüst
authors.forename: Tilo
authors.initials: T
authors.lastname: Kircher
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
mesh_terms: 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
chemical_list: D002352:Carrier Proteins; C475071:DAOA protein, human; D047908:Intracellular Signaling Peptides and Proteins