Positive association of dopamine D2 receptor polymorphism with bipolar affective disorder in a European Multicenter Association study of affective disorders

Isabelle Massat, Daniel Souery, Jurgen Del-Favero, Sofie Van Gestel, Alessandro Serretti, Fabio Macciardi, Enrico Smeraldi, Radka Kaneva, Rolf Adolfsson, Peter O. Nylander, Douglas Blackwood, Walter Muir, George N. Papadimitriou, Dimitris Dikeos, Lilijana Oru, Ronnen H. Segman, Sladjana Ivezi, Harold Aschauer, Manfred Ackenheil, S. FuchshuberHenrik Dam, Miro Jakovljevi, Leena Peltonen, Christiane Hilger, François Hentges, Luc Staner, Vihra Milanova, Elena Jazin, Bernard Lerer, Christine Van Broeckhoven, Julien Mendlewicz

Research output: Contribution to journalArticlepeer-review

Abstract

Convincing evidence for a genetic component in the etiology of affective disorders (AD), including bipolar affective disorder (BPAD) and unipolar affective disorder (UPAD), is supported by traditional and molecular genetic studies. Most arguments lead to the complex inheritance hypothesis, suggesting that the mode of inheritance is probably not Mendelian but most likely oligogenic (or polygenic) and that the contribution of genes could be moderate or weak. The purpose of the present European multicenter study (13 centers) was to test the potential role in BPAD and UPAD of two candidate dopaminergic markers, DRD2 and DRD3, using a case-control association design. The following samples were analyzed for DRD2: 358 BPAD/358 control (C) and 133 UPAD/133 C subjects, and for DRD3: 325 BPAD/325 C and 136 UPAD/136 C subjects. Patients and controls were individually matched for sex, age (±five years) and geographical origin. Evidence for significant association between BPAD and DRD2 emerged, with an over-representation of genotype 5-5 (P= 0.004) and allele 5 (P=0.002) in BPAD cases compared to controls. No association was found for DRD2 in UPAD, and for DRD3 neither in BPAD or UPAD. Our results suggest that the DRD2 microsatellite may be in linkage disequilibrium with a nearby genetic variant involved in the susceptibility to BPAD. Our large European sample allowed for replicating of some previous reported positive findings obtained in other study populations.

Original languageEnglish
Pages (from-to)177-185
Number of pages9
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume114
Issue number2
DOIs
Publication statusPublished - Mar 8 2002

Keywords

  • Affective disorders
  • Association study
  • Bipolar affective disorder
  • Candidate gene
  • Dopamine D2 receptor
  • Dopamine D3 receptor
  • DRD2
  • DRD3
  • Unipolar affective disorder

ASJC Scopus subject areas

  • Genetics(clinical)
  • Neuropsychology and Physiological Psychology
  • Neuroscience(all)

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