Family-based association analysis to finemap bipolar linkage peak on chromosome 8q24 using 2,500 genotyped SNPs and 15,000 imputed SNPs

Peng Zhang, Nan Xiang, Yi Chen, Elzbieta Śliwerska, Melvin G. McInnis, Margit Burmeister, Sebastian Zöllner

    Research output: Contribution to journalArticle

    Abstract

    Objective: Multiple linkage and association studies have suggested chromosome 8q24 as a promising candidate region for bipolar disorder (BP). We performed a detailed association analysis assessing the contribution of common genetic variation in this region to the risk of BP.Methods: We analyzed 2,756 single nucleotide polymorphism (SNP) markers in the chromosome 8q24 region of 3,512 individuals from 737 families. In addition, we extended genotype imputation methods to family-based data and imputed 22,725 HapMap SNPs in the same region on 8q24. We applied a family-based method to test 15,552 high-quality genotyped or imputed SNPs for association with BP.Results: Our association analysis identified the most significant marker (p = 4.80 × 10-5), near the gene encoding potassium voltage-gated channel KQT-like protein (KCNQ3). Other marginally significant markers were located near adenylate cyclase 8 (ADCY8) and ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3GAL1).Conclusions: We developed an approach to apply MACH imputation to family-based data, which can increase the power to detect association signals. Our association results showed suggestive evidence of association of BP with loci near KCNQ3, ADCY8, and ST3GAL1. Consistent with genes identified by genome-wide association studies for BP, our results suggest the involvement of ion channelopathy in BP pathogenesis. However, common variants are insufficient to explain linkage findings in 8q24; other genetic variation should be explored.

    Original languageEnglish (US)
    Pages (from-to)786-792
    Number of pages7
    JournalBipolar Disorders
    Volume12
    Issue number8
    DOIs
    StatePublished - Dec 1 2010

    Keywords

    • 8q24
    • Bipolar disorder
    • Imputation
    • Ion channelopathy

    ASJC Scopus subject areas

    • Psychiatry and Mental health
    • Biological Psychiatry

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