Linkage of bipolar affective disorder on chromosome 8q24: Follow-up and parametric analysis

Dimitrios Avramopoulos, V. L. Willour, Peter P Zandi, Y. Huo, Dean F Mackinnon, James Bennett Potash, J Raymond Depaulo, M. G. McInnis

Research output: Contribution to journalArticle

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).

Original languageEnglish (US)
Pages (from-to)191-196
Number of pages6
JournalMolecular Psychiatry
Volume9
Issue number2
DOIs
StatePublished - 2004

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Keywords

  • Adenylate cyclase
  • Bipolar disorder
  • Genes
  • Linkage (genetics)
  • Potassium channels
  • Thyroglobulin

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

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