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

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 153B; no. 8; pp. 1425 - 1433
• Main Authors: Mathieu, Flavie, Dizier, Marie-Hélène, Etain, Bruno, Jamain, Stéphane, Rietschel, Marcella, Maier, Wolfgang, Albus, Margot, McKeon, Patrick, Roche, Siobhan, Blackwood, Douglas, Muir, Walter J., Henry, Chantal, Malafosse, Alain, Preisig, Martin, Ferrero, François, Cichon, Sven, Schumacher, Johannes, Ohlraun, Stephanie, Propping, Peter, Abou Jamra, Rami, Schulze, Thomas G., Zelenica, Diana, Charon, Céline, Marusic, Andrej, Dernovsek, Mojca C., Gurling, Hugh, Nöthen, Markus, Lathrop, Mark, Leboyer, Marion, Bellivier, Frank
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-12-2010; Wiley-Liss
• Subjects: Adolescent; Adult and adolescent clinical studies; Age; age at onset; Age of Onset; Biological and medical sciences; Bipolar disorder; Bipolar Disorder - epidemiology; Bipolar Disorder - genetics; Bipolar disorders; Chromosome Mapping; Chromosomes, Human, Pair 2 - genetics; Classical genetics, quantitative genetics, hybrids; Data Interpretation, Statistical; Europe; Female; Fundamental and applied biological sciences. Psychology; Gene polymorphism; Genetic Association Studies; Genetic factors; Genetic Heterogeneity; Genetic Linkage; Genetic Markers; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Genomes; Genotype; Heredity; Human; Humans; Linkage analysis; Male; Medical genetics; Medical sciences; Miscellaneous; Mood disorders; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Young Adult; Europe; Mood disorder; Genetic mapping; Heterogeneity; Age of onset; Genetics; Early; Bipolar disorder; European; age at onset; genetic heterogeneity
• ISSN: 1552-4841; 1552-485X; 1552-485X
• DOI: 10.1002/ajmg.b.31121

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.