European collaborative study of early-onset bipolar disorder: Evidence for genetic heterogeneity on 2q14 according to age at onset

Flavie Mathieu, Marie Hélène Dizier, Bruno Etain, Stéphane Jamain, Marcella Rietschel, Wolfgang Maier, Margot Albus, Patrick McKeon, Siobhan Roche, Douglas Blackwood, Walter J. Muir, Chantal Henry, Alain Malafosse, Martin Preisig, François Ferrero, Sven Cichon, Johannes Schumacher, Stephanie Ohlraun, Peter Propping, Rami Abou JamraThomas G. Schulze, Diana Zelenica, Céline Charon, Andrej Marusic, Mojca C. Dernovsek, Hugh Gurling, Markus Nöthen, Mark Lathrop, Marion Leboyer, Frank Bellivier

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Bipolar disorder has a genetic component, but the mode of inheritance remains unclear. A previous genome scan conducted in 70 European families led to detect eight regions linked to bipolar disease. Here, we present an investigation of whether the phenotypic heterogeneity of the disorder corresponds to genetic heterogeneity in these regions using additional markers and an extended sample of families. The MLS statistic was used for linkage analyses. The predivided sample test and the maximum likelihood binomial methods were used to test genetic homogeneity between early-onset bipolar type I (cut-off of 22 years) and other types of the disorder (later onset of bipolar type I and early-onset bipolar type II), using a total of 138 independent bipolar-affected sib-pairs. Analysis of the extended sample of families supports linkage in four regions (2q14, 3p14, 16p23, and 20p12) of the eight regions of linkage suggested by our previous genome scan. Heterogeneity testing revealed genetic heterogeneity between early and late-onset bipolar type I in the 2q14 region (P=0.0001). Only the early form of the bipolar disorder but not the late form appeared to be linked to this region. This region may therefore include a genetic factor either specifically involved in the early-onset bipolar type I or only influencing the age at onset (AAO). Our findings illustrate that stratification according to AAO may be valuable for the identification of genetic vulnerability polymorphisms.

Original languageEnglish (US)
Pages (from-to)1425-1433
Number of pages9
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Issue number8
StatePublished - Dec 2010
Externally publishedYes


  • Age at onset
  • Bipolar disorder
  • Genetic heterogeneity

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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