G72 and its association with major depression and neuroticism in large population-based groups from Germany

Marcella Rietschel, Lars Beckmann, Jana Strohmaier, Alexander Georgi, Anna Karpushova, Frederike Schirmbeck, Katja V. Boesshenz, Christine Schmäl, Christin Bürger, Rami Abou Jamra, Johannes Schumacher, Susanne Höfels, Robert Kumsta, Sonja Entringer, Axel Krug, Valentin Markov, Wolfgang Maier, Peter Propping, Stefan Wüst, Tilo KircherMarkus M. Nöthen, Sven Cichon, Thomas G. Schulze

Research output: Contribution to journalArticle

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. Method: 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.

Original languageEnglish (US)
Pages (from-to)753-762
Number of pages10
JournalAmerican Journal of Psychiatry
Volume165
Issue number6
DOIs
StatePublished - Jun 2008
Externally publishedYes

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Population Groups
Haplotypes
Germany
Depression
Panic Disorder
Bipolar Disorder
Schizophrenia
Neuroticism
Cluster Analysis
Anxiety
Population
Genes

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Rietschel, M., Beckmann, L., Strohmaier, J., Georgi, A., Karpushova, A., Schirmbeck, F., ... Schulze, T. G. (2008). G72 and its association with major depression and neuroticism in large population-based groups from Germany. American Journal of Psychiatry, 165(6), 753-762. https://doi.org/10.1176/appi.ajp.2008.07060883

G72 and its association with major depression and neuroticism in large population-based groups from Germany. / Rietschel, Marcella; Beckmann, Lars; Strohmaier, Jana; Georgi, Alexander; Karpushova, Anna; Schirmbeck, Frederike; Boesshenz, Katja V.; Schmäl, Christine; Bürger, Christin; Jamra, Rami Abou; Schumacher, Johannes; Höfels, Susanne; Kumsta, Robert; Entringer, Sonja; Krug, Axel; Markov, Valentin; Maier, Wolfgang; Propping, Peter; Wüst, Stefan; Kircher, Tilo; Nöthen, Markus M.; Cichon, Sven; Schulze, Thomas G.

In: American Journal of Psychiatry, Vol. 165, No. 6, 06.2008, p. 753-762.

Research output: Contribution to journalArticle

Rietschel, M, Beckmann, L, Strohmaier, J, Georgi, A, Karpushova, A, Schirmbeck, F, Boesshenz, KV, Schmäl, C, Bürger, C, Jamra, RA, Schumacher, J, Höfels, S, Kumsta, R, Entringer, S, Krug, A, Markov, V, Maier, W, Propping, P, Wüst, S, Kircher, T, Nöthen, MM, Cichon, S & Schulze, TG 2008, 'G72 and its association with major depression and neuroticism in large population-based groups from Germany', American Journal of Psychiatry, vol. 165, no. 6, pp. 753-762. https://doi.org/10.1176/appi.ajp.2008.07060883
Rietschel, Marcella ; Beckmann, Lars ; Strohmaier, Jana ; Georgi, Alexander ; Karpushova, Anna ; Schirmbeck, Frederike ; Boesshenz, Katja V. ; Schmäl, Christine ; Bürger, Christin ; Jamra, Rami Abou ; Schumacher, Johannes ; Höfels, Susanne ; Kumsta, Robert ; Entringer, Sonja ; Krug, Axel ; Markov, Valentin ; Maier, Wolfgang ; Propping, Peter ; Wüst, Stefan ; Kircher, Tilo ; Nöthen, Markus M. ; Cichon, Sven ; Schulze, Thomas G. / G72 and its association with major depression and neuroticism in large population-based groups from Germany. In: American Journal of Psychiatry. 2008 ; Vol. 165, No. 6. pp. 753-762.
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AU - Rietschel, Marcella

AU - Beckmann, Lars

AU - Strohmaier, Jana

AU - Georgi, Alexander

AU - Karpushova, Anna

AU - Schirmbeck, Frederike

AU - Boesshenz, Katja V.

AU - Schmäl, Christine

AU - Bürger, Christin

AU - Jamra, Rami Abou

AU - Schumacher, Johannes

AU - Höfels, Susanne

AU - Kumsta, Robert

AU - Entringer, Sonja

AU - Krug, Axel

AU - Markov, Valentin

AU - Maier, Wolfgang

AU - Propping, Peter

AU - Wüst, Stefan

AU - Kircher, Tilo

AU - Nöthen, Markus M.

AU - Cichon, Sven

AU - Schulze, Thomas G.

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N2 - 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. Method: 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.

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