Mutational screening and association study of glutamate decarboxylase 1 as a candidate susceptibility gene for bipolar affective disorder and schizophrenia
Recent evidence from postmortem studies suggests that GAD1 encoding the gamma‐aminobutyric acid (GABA) synthetic enzyme GAD67 is a functional candidate susceptibility gene for both bipolar affective disorder (BPAD) and schizophrenia. Previous studies suggest linkage between D2S326 near GAD1 and BPAD...
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Published in | American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 135B; no. 1; pp. 94 - 101 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
05.05.2005
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Subjects | |
Online Access | Get full text |
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Summary: | Recent evidence from postmortem studies suggests that GAD1 encoding the gamma‐aminobutyric acid (GABA) synthetic enzyme GAD67 is a functional candidate susceptibility gene for both bipolar affective disorder (BPAD) and schizophrenia. Previous studies suggest linkage between D2S326 near GAD1 and BPAD. We systematically screened GAD1 exons, flanking intronic sequences, and the promoter sequence for polymorphisms in 16 BPAD patients and five controls from Denmark. We identified eight single nucleotide polymorphisms (SNPs) including two in the promoter sequence. An association study of SNPs covering GAD1 was performed in a Danish sample of 82 BPAD subjects and 120 controls and in a Scottish sample of 197 individuals with schizophrenia, 200 BPAD subjects and 199 controls. Linkage disequilibrium (LD) and haplotype frequencies were estimated from genotype data from eight SNPs. Strong pairwise LD was observed among all pairs of neighboring markers. In the Danish sample, we found weak association between BPAD and two promoter SNPs spaced 1 kb apart. Furthermore, one, two, and three loci haplotype analysis showed weak association with BPAD in the Danish sample. The results from the association studies indicate that promoter variants are of importance for the Danish BPAD cases and we cannot reject the hypothesis of GAD1 as a functional candidate gene for BPAD. No association was observed between BPAD or schizophrenia and any of the investigated SNPs in the Scottish sample set. Thus the results obtained from the Scottish sample suggest that the GAD1 gene variants do not play a major role in the predisposition to schizophrenia. © 2005 Wiley‐Liss, Inc. |
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Bibliography: | The Lundbeck Foundation - No. 39/98; No. 59/99 Ministry of Education, Culture, and Research The Danish Medical Research Council - No. 9601887; No. 9902769 Simon Fougner Hartmann Foundation ark:/67375/WNG-HP5M62ZC-C M.D. Lundorf and H.N. Buttenschøn contributed equally to this work. Ingeborg and Leo Dannin Eilif Trier-Hansen Foundation In respectful memory of Prof. Henrik Ewald (1958-2004). istex:591CF8495C705E5AE38AB52F338DACA33A7100BA Dagmar Marshall Foundation Einer Geert-Jorgensens Foundation ArticleID:AJMG30137 Psykiatrisk Forskningsfond In respectful memory of Prof. Henrik Ewald (1958–2004). ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1552-4841 1552-485X |
DOI: | 10.1002/ajmg.b.30137 |