Family-based SNP association study on 8q24 in bipolar disorder

Peter P. Zandi, Sebastian Zöllner, Dimitrios Avramopoulos, Virginia L. Willour, Yi Chen, Zhaohui S. Qin, Margit Burmeister, Kuangyi Miao, Shyam Gopalakrishnan, Richard McEachin, James B. Potash, J. Raymond DePaulo, Melvin G. McInnis

Research output: Contribution to journalArticlepeer-review

Abstract

Previous linkage studies have identified chromosome 8q24 as a promising positional candidate region to search for bipolar disorder (BP) susceptibility genes. We, therefore, sought to identify BP susceptibility genes on chromosome 8q24 using a family-based association study of a dense panel of SNPs selected to tag the known common variation across the region of interest. A total of 1,458 SNPs across 16 Mb of 8q24 were examined in 3,512 subjects, 1,954 of whom were affected with BP, from 737 multiplex families. Single-locus tests were carried out with FBAT and Geno-PDT, and multi-locus test were carried out with HBAT and multi-locus Geno-PDT. None of the SNPs were associated with BP in the single-locus tests at a level that exceeded our threshold for study-wide significance (P < 3.00 × 10-5). However, there was consistent evidence at our threshold for the suggestive level (P < 7.00 × 10-4) from both the single locus and multi-locus tests of associations with SNPs in the genes ADCY8, ST3GAL1, and NSE2. Multi-locus analyses suggested joint effects between ADCY8 and ST3GAL1 (P = 3.00 × 10-4), with at least one copy of the "high risk" allele required at both genes for association with BP, consistent with a jointly dominant-dominant model of action. These findings with ADCY8 and ST3GAL1 warrant further investigation in order to confirm the observed associations and their functional significance for BP susceptibility.

Original languageEnglish (US)
Pages (from-to)612-618
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume147
Issue number5
DOIs
StatePublished - Jul 5 2008

Keywords

  • Bipolar disorder
  • Chromosome 8q24
  • Dominant-dominant model
  • Genetic association

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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