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

Mathieu, Flavie
Dizier, Marie-Helene
Etain, Bruno
Jamain, Stephane
Rietschel, Marcella
Maier, Wolfgang
Albus, Margot
McKeon, Patrick
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Published in American Journal of Medical Genetics. B. 2010, vol. 153B, no. 8, p. 1425-1433
Abstract 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. (c) 2010 Wiley-Liss, Inc.
Keywords Adolescent*Age of OnsetBipolar Disorder/epidemiology/*geneticsChromosome MappingChromosomes, Human, Pair 2/*geneticsData Interpretation, StatisticalEuropeFemaleGenetic Association Studies*Genetic Heterogeneity*Genetic LinkageGenetic MarkersGenetic Predisposition to DiseaseGenotypeHumansMaleYoung Adult
PMID: 20886542
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Research group Génétique psychiatrique (4)
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MATHIEU, Flavie et al. European collaborative study of early-onset bipolar disorder: Evidence for genetic heterogeneity on 2q14 according to age at onset. In: American Journal of Medical Genetics. B, 2010, vol. 153B, n° 8, p. 1425-1433. doi: 10.1002/ajmg.b.31121 https://archive-ouverte.unige.ch/unige:21124

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Deposited on : 2012-05-23

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