title: European collaborative study of early-onset bipolar disorder: Evidence for genetic heterogeneity on 2q14 according to age at onset.
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. © 2010 Wiley-Liss, Inc.
authors.affiliation: INSERM, U 955, IMRB, Department of Medical Genetics, Psychiatry Genetics, Creteil, France. flavie.mathieu@inserm.fr
authors.forename: Flavie
authors.initials: F
authors.lastname: Mathieu
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Dizier
authors.forename: Bruno
authors.initials: B
authors.lastname: Etain
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jamain
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Margot
authors.initials: M
authors.lastname: Albus
authors.forename: Patrick
authors.initials: P
authors.lastname: McKeon
authors.forename: Siobhan
authors.initials: S
authors.lastname: Roche
authors.forename: Douglas
authors.initials: D
authors.lastname: Blackwood
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Muir
authors.forename: Chantal
authors.initials: C
authors.lastname: Henry
authors.forename: Alain
authors.initials: A
authors.lastname: Malafosse
authors.forename: Martin
authors.initials: M
authors.lastname: Preisig
authors.forename: François
authors.initials: F
authors.lastname: Ferrero
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ohlraun
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Rami
authors.initials: R
authors.lastname: Abou Jamra
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
authors.forename: Diana
authors.initials: D
authors.lastname: Zelenica
authors.forename: Céline
authors.initials: C
authors.lastname: Charon
authors.forename: Andrej
authors.initials: A
authors.lastname: Marusic
authors.forename: Mojca C
authors.initials: MC
authors.lastname: Dernovsek
authors.forename: Hugh
authors.initials: H
authors.lastname: Gurling
authors.forename: Markus
authors.initials: M
authors.lastname: Nöthen
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.forename: Frank
authors.initials: F
authors.lastname: Bellivier
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics*; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003627:Data Interpretation, Statistical; D005060:Europe; D005260:Female; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D005819:Genetic Markers