Journal article
Linkage of bipolar affective disorder on chromosome 8q24: follow-up and parametric analysis
Molecular psychiatry, Vol.9(2), pp.191-196
2004
DOI: 10.1038/sj.mp.4001388
PMID: 14966477
Abstract
Our group first reported a linkage finding for bipolar (BP) disorder on chromosome 8q24 in a study of 50 multiplex pedigrees, with an HLOD score reaching 2.39. Recently, Cichon et al reported an LOD score of 3.62 in the same region using two-point parametric analysis. Subsequently, we published the results of a genome scan for linkage to BP disorder using a sample extended to 65 pedigrees in which chromosome 8q24 provided the best finding, an NPL score of 3.13, approaching the accepted score for suggestive linkage. We have now fine mapped this region of chromosome 8 in our 65 pedigrees by the addition of 19 microsatellite markers reaching a marker density of 0.8 cM and an information content of 0.84. After the addition of the new data, the original NPL score slightly increased to 3.25. Two-point parametric analysis using the model employed by Cichon et al obtained an LOD score of 3.32 for marker D8S256 at θ=0.14 exceeding the proposed threshold for genomewide significance. After adjusting the parameters in accordance with the ‘common disease–common variant’ hypothesis, multipoint parametric analysis resulted in an HLOD of 2.49 (α=0.78) between D8S529 and D8S256, and defined a 1-LOD interval corresponding to a 2.3 Mb region. No allelic association with the disease was observed for our set of microsatellite markers. Biologically, plausible candidate genes in this region include thyroglobulin, KCNQ3 coding for a voltage-gated potassium channel and the gene for brain adenyl-cyclase (ADCY8).
Details
- Title: Subtitle
- Linkage of bipolar affective disorder on chromosome 8q24: follow-up and parametric analysis
- Creators
- D AVRAMOPOULOS - Department of Psychiatry, Johns Hopkins University, School of Medicine, North Wolfe Street, Baltimore, MD 21287, United StatesV. L WILLOUR - Department of Psychiatry, Johns Hopkins University, School of Medicine, North Wolfe Street, Baltimore, MD 21287, United StatesP. P ZANDI - Department of Mental Health, Johns Hopkins University, School of Public Health, N., Broadway, Baltimore, MD 21205, United StatesY HUO - Department of Psychiatry, Johns Hopkins University, School of Medicine, North Wolfe Street, Baltimore, MD 21287, United StatesD. F MACKINNON - Department of Psychiatry, Johns Hopkins University, School of Medicine, North Wolfe Street, Baltimore, MD 21287, United StatesJ. B POTASH - Department of Psychiatry, Johns Hopkins University, School of Medicine, North Wolfe Street, Baltimore, MD 21287, United StatesJ. R DEPAULO - Department of Psychiatry, Johns Hopkins University, School of Medicine, North Wolfe Street, Baltimore, MD 21287, United StatesM. G MCINNIS - Department of Psychiatry, Johns Hopkins University, School of Medicine, North Wolfe Street, Baltimore, MD 21287, United States
- Resource Type
- Journal article
- Publication Details
- Molecular psychiatry, Vol.9(2), pp.191-196
- Publisher
- Nature Publishing Group; Basingstoke
- DOI
- 10.1038/sj.mp.4001388
- PMID
- 14966477
- ISSN
- 1359-4184
- eISSN
- 1476-5578
- Language
- English
- Date published
- 2004
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984070525402771
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