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  • Original Research Article
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Linkage of bipolar affective disorder on chromosome 8q24: follow-up and parametric analysis

Molecular Psychiatry volume 9, pages 191–196 (2004)Cite this article

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).

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Acknowledgements

This work was supported by grants from the National Institute of Mental Health, the Stanley Medical Research Institute, the National Alliance for Research on Schizophrenia and Depression, the Alex. Brown & Sons Charitable Foundation, and the Charles A. Dana Foundation program ‘The Dana Consortium on the Genetic Basis of Manic Depressive Illness’. We would like to thank Dr Francis J McMahon and Dr Sylvia G Simpson for their participation in the clinical evaluations and Tyra Diggs for providing technical support.

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Author notes

  1. D Avramopoulos and V L Willour: The first two authors contributed equally to the work.

Authors and Affiliations

  1. Department of Psychiatry, Johns Hopkins University, School of Medicine, North Wolfe Street, Baltimore, 21287, MD, USA

    D Avramopoulos, V L Willour, Y Huo, D F MacKinnon, J B Potash, J R DePaulo Jr & M G McInnis

  2. Department of Mental Health, Johns Hopkins University, School of Public Health, N. Broadway, Baltimore, 21205, MD, USA

    P P Zandi

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  1. D Avramopoulos
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Correspondence to D Avramopoulos.

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Avramopoulos, D., Willour, V., Zandi, P. et al. Linkage of bipolar affective disorder on chromosome 8q24: follow-up and parametric analysis. Mol Psychiatry 9, 191–196 (2004). https://doi.org/10.1038/sj.mp.4001388

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