Dataset Information

Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14.

ABSTRACT: Preliminary studies suggested that age at onset (AAO) may help to define homogeneous bipolar affective disorder (BPAD) subtypes. This candidate symptom approach might be useful to identify vulnerability genes. Thus, the probability of detecting major disease-causing genes might be increased by focusing on families with early-onset BPAD type I probands. This study was conducted as part of the European Collaborative Study of Early Onset BPAD (France, Germany, Ireland, Scotland, Switzerland, England, Slovenia). We performed a genome-wide search with 384 microsatellite markers using non-parametric linkage analysis in 87 sib-pairs ascertained through an early-onset BPAD type I proband (AAO of 21 years or below). Non-parametric multipoint analysis suggested eight regions of linkage with P-values<0.01 (2p21, 2q14.3, 3p14, 5q33, 7q36, 10q23, 16q23 and 20p12). The 3p14 region showed the most significant linkage (genome-wide P-value estimated over 10 000 simulated replicates of 0.015 [0.01-0.02]). After genome-wide search analysis, we performed additional linkage analyses with increased marker density using markers in four regions suggestive for linkage and having an information contents lower than 75% (3p14, 10q23, 16q23 and 20p12). For these regions, the information content improved by about 10%. In chromosome 3, the non-parametric linkage score increased from 3.51 to 3.83. This study is the first to use early-onset bipolar type I probands in an attempt to increase sample homogeneity. These preliminary findings require confirmation in independent panels of families.

SUBMITTER: Etain B

PROVIDER: S-EPMC1959341 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

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Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14.

Etain B B Mathieu F F Rietschel M M Maier W W Albus M M McKeon P P Roche S S Kealey C C Blackwood D D Muir W W Bellivier F F Henry C C Dina C C Gallina S S Gurling H H Malafosse A A Preisig M M Ferrero F F Cichon S S Schumacher J J Ohlraun S S Borrmann-Hassenbach M M Propping P P Abou Jamra R R Schulze T G TG Marusic A A Dernovsek Z M ZM Giros B B Bourgeron T T Lemainque A A Bacq D D Betard C C Charon C C Nöthen M M MM Lathrop M M Leboyer M M

Molecular psychiatry 20060314 7

Preliminary studies suggested that age at onset (AAO) may help to define homogeneous bipolar affective disorder (BPAD) subtypes. This candidate symptom approach might be useful to identify vulnerability genes. Thus, the probability of detecting major disease-causing genes might be increased by focusing on families with early-onset BPAD type I probands. This study was conducted as part of the European Collaborative Study of Early Onset BPAD (France, Germany, Ireland, Scotland, Switzerland, Englan ...[more]

PMID: 16534504

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Project description:Using behavioral and genetic information from the Autism Genetics Resource Exchange (AGRE) data set we developed phenotypes and investigated linkage and association for individuals with and without Autism Spectrum Disorders (ASD) who exhibit expressive language behaviors consistent with a motor speech disorder. Speech and language variables from Autism Diagnostic Interview-Revised (ADI-R) were used to develop a motor speech phenotype associated with non-verbal or unintelligible verbal behaviors (NVMSD:ALL) and a related phenotype restricted to individuals without significant comprehension difficulties (NVMSD:C). Using Affymetrix 5.0 data, the PPL framework was employed to assess the strength of evidence for or against trait-marker linkage and linkage disequilibrium (LD) across the genome. Ingenuity Pathway Analysis (IPA) was then utilized to identify potential genes for further investigation. We identified several linkage peaks based on two related language-speech phenotypes consistent with a potential motor speech disorder: chromosomes 1q24.2, 3q25.31, 4q22.3, 5p12, 5q33.1, 17p12, 17q11.2, and 17q22 for NVMSD:ALL and 4p15.2 and 21q22.2 for NVMSD:C. While no compelling evidence of association was obtained under those peaks, we identified several potential genes of interest using IPA. CONCLUSION: Several linkage peaks were identified based on two motor speech phenotypes. In the absence of evidence of association under these peaks, we suggest genes for further investigation based on their biological functions. Given that autism spectrum disorders are complex with a wide range of behaviors and a large number of underlying genes, these speech phenotypes may belong to a group of several that should be considered when developing narrow, well-defined, phenotypes in the attempt to reduce genetic heterogeneity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11689-010-9063-2) contains supplementary material, which is available to authorized users.

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Dataset Information

Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14.

Publications

Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14.

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