1. European collaborative study of early-onset bipolar disorder: Evidence for genetic heterogeneity on 2q14 according to age at onset
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Mathieu, Flavie, Dizier, Marie-Hélène, Etain, Bruno, Jamain, Stéphane, Rietschel, Marcella, Maier, Wolfgang, Albus, Margot, Mckeon, Patrick, Roche, Siobhan, Blackwood, Douglas, Muir, Walter, Henry, Chantal, Malafosse, Alain, Preisig, Martin, Ferrero, François, Cichon, Sven, Schumacher, Johannes, Ohlraun, Stephanie, Propping, Peter, Abou Jamra, Rami, Schulze, Thomas, Zelenica, Diana, Charon, Céline, Marusic, Andrej, Dernovsek, Mojca, Gurling, Hugh, Nöthen, Markus, Lathrop, Mark, Leboyer, Marion, Bellivier, Frank, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Fondation FondaMental [Créteil], Variabilité Génétique et Maladies Humaines, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Centre d'Etude du Polymorphisme Humain (CEPH), Université Paris Diderot - Paris 7 (UPD7)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Division Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Department of Psychiatry, Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Psychiatry and Psychotherapy, District Hospital Haar, St. Patrick's Hospital, Smurfit Institute of Genetics, Trinity College Dublin, Division of Psychiatry, University of Edinburgh-Royal Edinburgh Hospital, Urgence et post-urgence psychiatrique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Department of psychiatry, University Hospital - Lausanne, Geneva University Hospital (HUG), Center for Human Genetic Research, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Institute of Human Genetics, Georg-August-University [Göttingen], Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institute of Public Health of the Republic of Slovenia, University Psychiatric Hospital, Department of psychiatry and behavioural Sciences, Windeyer Institute for Medical Sciences-Royal Free and University College London Medical School, Grant sponsor: INSERM, Grant sponsor: Assistance Publique des Hôpitaux de Paris, Grant sponsor: Agence Nationale pour la Recherche (ANR-Project Manage-BP), Grant sponsor: National Alliance for Research on Schizophrenia and Depression (NARSAD), Grant sponsor: Fondation pour la Recherche sur le Cerveau (FRC), Grant sponsor: RTRS Santé Mentale (FondaMental), Grant sponsor: National Genomic Network (NGFN) of the German Ministry of Education and Research, Grant sponsor: Deutsche Forschungsgemeinschaft (SFB 400 Subprojects D1 and D3, Graduiertenkolleg GRK 246, FOR 423 Subproject D1), Grant sponsor: Alfried Krupp von Bohlen und Halbach-Stiftung, Grant sponsor: Interuniversity Attraction Poles program P5/19 of the Belgian Federal Science Policy Office, Grant sponsor: German Research Society (Grant Numbers: AL 230-1/2/3-230-5/1/2, SFB 400), Grant sponsor: Aware, Grant sponsor: Health Research Board (Grant Number: H01069 HRB RP153/2000), Grant sponsor: Friends of St. Patrick‟s Hospital, and Grant sponsor: Swiss National Foundation ( Grant Numbers: 32-40677.94, 32-47315.96, 32-061974.00, 32-66793.01, 32-102168.03).
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MESH: Adolescent ,MESH: Humans ,Bipolar disorder ,MESH: Age of Onset ,MESH: Genetic Linkage ,MESH: Genetic Predisposition to Disease ,MESH: Chromosomes, Human, Pair 2 ,MESH: Genetic Heterogeneity ,MESH: Genetic Markers ,MESH: Male ,genetic heterogeneity ,MESH: Genotype ,MESH: Young Adult ,MESH: Bipolar Disorder ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,MESH: Europe ,MESH: Chromosome Mapping ,age at onset ,MESH: Data Interpretation, Statistical ,MESH: Female ,MESH: Genetic Association Studies - Abstract
International audience; 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.
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- 2010