European collaborative study of early-onset bipolar disorder: Evidence for genetic heterogeneity on 2q14 according to age at onset.
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.
Mathieu
Flavie
F
INSERM, U 955, IMRB, Department of Medical Genetics, Psychiatry Genetics, Creteil, France. flavie.mathieu@inserm.fr
Dizier
Marie-Hélène
MH
Etain
Bruno
B
Jamain
Stéphane
S
Rietschel
Marcella
M
Maier
Wolfgang
W
Albus
Margot
M
McKeon
Patrick
P
Roche
Siobhan
S
Blackwood
Douglas
D
Muir
Walter J
WJ
Henry
Chantal
C
Malafosse
Alain
A
Preisig
Martin
M
Ferrero
François
F
Cichon
Sven
S
Schumacher
Johannes
J
Ohlraun
Stephanie
S
Propping
Peter
P
Abou Jamra
Rami
R
Schulze
Thomas G
TG
Zelenica
Diana
D
Charon
Céline
C
Marusic
Andrej
A
Dernovsek
Mojca C
MC
Gurling
Hugh
H
Nöthen
Markus
M
Lathrop
Mark
M
Leboyer
Marion
M
Bellivier
Frank
F
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
D005819:Genetic Markers