Mathieu and Dizier contributed equally to this work.
Article first published online: 30 SEP 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 153B, Issue 8, pages 1425–1433, December 2010
How to Cite
Mathieu, F., Dizier, M.-H., Etain, B., Jamain, S., Rietschel, M., Maier, W., Albus, M., McKeon, P., Roche, S., Blackwood, D., Muir, W. J., Henry, C., Malafosse, A., Preisig, M., Ferrero, F., Cichon, S., Schumacher, J., Ohlraun, S., Propping, P., Abou Jamra, R., Schulze, T. G., Zelenica, D., Charon, C., Marusic, A., Dernovsek, M. C., Gurling, H., Nöthen, M., Lathrop, M., Leboyer, M. and Bellivier, F. (2010), European collaborative study of early-onset bipolar disorder: Evidence for genetic heterogeneity on 2q14 according to age at onset. Am. J. Med. Genet., 153B: 1425–1433. doi: 10.1002/ajmg.b.31121
How to Cite this Article: Mathieu F, Dizier MH, Etain B, Jamain S, Rietschel M, Maier W, Albus M, McKeon P, Roche S, Blackwood D, Muir W, Henry C, Malafosse A, Preisig M, Ferrero F, Cichon S, Schumacher J, Ohlraun S, Propping P, Abou Jamra R, Schulze TG, Zelenica D, Charon C, Marusic A, Dernovsek ZM, Nöthen M, Lathrop M, Leboyer M, Bellivier F. 2010. European Collaborative Study of Early-Onset Bipolar Disorder: Evidence for Genetic Heterogeneity on 2q14 According to Age at Onset. Am J Med Genet Part B 153B:1425–1433.
- Issue published online: 25 NOV 2010
- Article first published online: 30 SEP 2010
- Manuscript Accepted: 3 AUG 2010
- Manuscript Received: 27 OCT 2009
- Assistance Publique des Hôpitaux de Paris
- Agence Nationale pour la Recherche (ANR—Project Manage-BP)
- National Alliance for Research on Schizophrenia and Depression (NARSAD)
- Fondation pour la Recherche sur le Cerveau (FRC)
- RTRS Santé Mentale (FondaMental)
- National Genomic Network (NGFN) of the German Ministry of Education and Research
- Deutsche Forschungsgemeinschaft (SFB 400 Subprojects D1 and D3, Graduiertenkolleg GRK 246, FOR 423 Subproject D1)
- Alfried Krupp von Bohlen und Halbach-Stiftung
- Interuniversity Attraction Poles program P5/19 of the Belgian Federal Science Policy Office
- German Research Society. Grant Numbers: AL 230-1/2/3–230-5/1/2, SFB 400
- Health Research Board. Grant Number: H01069 HRB RP153/2000
- Friends of St. Patrick's Hospital
- Swiss National Foundation. Grant Numbers: 32-40677.94, 32-47315.96, 32-061974.00, 32-66793.01, 32-102168.03
- bipolar disorder;
- genetic heterogeneity;
- 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.