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Fine mapping of candidate regions for bipolar disorder provides strong evidence for susceptibility loci on chromosomes 7q

Authors

  • Haiyan Xu,

    1. Department of Genetics and Development, Columbia University, New York, New York
    2. Columbia Genome Center, Columbia University, New York, New York
    Current affiliation:
    1. Centre for Molecular Epidemiology, National University of Singapore, Singapore.
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  • Rong Cheng Ph.D.,

    Corresponding author
    1. Columbia Genome Center, Columbia University, New York, New York
    Current affiliation:
    1. Taub Institute, Columbia University, New York, NY.
    • Taub Institute, Columbia University, 630 West 168th Street, New York NY 10032.
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  • Suh-Hang Juo,

    1. Columbia Genome Center, Columbia University, New York, New York
    2. Department of Epidemiology, Columbia University, New York, New York
    3. Graduate Institute of Medical Genetics, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Jianjun Liu,

    1. Columbia Genome Center, Columbia University, New York, New York
    Current affiliation:
    1. Genome Institute of Singapore, Singapore, Singapore.
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  • Jo Ellen Loth,

    1. Department of Psychiatry, Columbia University, New York, New York
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  • Jean Endicott,

    1. Department of Psychiatry, Columbia University, New York, New York
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  • Conrad Gilliam,

    1. Department of Genetics and Development, Columbia University, New York, New York
    2. Columbia Genome Center, Columbia University, New York, New York
    Current affiliation:
    1. Department of Human Genetics, University of Chicago, Chicago, IL.
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  • Miron Baron

    1. Columbia Genome Center, Columbia University, New York, New York
    2. Department of Psychiatry, Columbia University, New York, New York
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  • How to Cite this Article: Xu H, Cheng R, Juo S-H, Liu J, Loth JE, Endicott J, Gilliam C, Baron M. 2011. Fine Mapping of Candidate Regions for Bipolar Disorder Provides Strong Evidence for Susceptibility Loci on Chromosomes 7q. Am J Med Genet Part B 156:168–176.

Abstract

Genomewide scans of bipolar disorder (BP) have not produced consistent linkage findings. Follow-up studies using enlarged samples and enhanced marker density can bolster or refute claims of linkage and pave the way to gene discovery. We conducted linkage and association analyses, using a ∼3-cM density map of 10 candidate regions, in a large BP pedigree sample (865 individuals from 56 pedigrees). The candidate regions were identified in a previous 10-cM genome-wide scan using a subset of this sample (373 individuals from 40 pedigrees). The present sample consists of the expanded original pedigrees (“core” pedigrees) and 16 additional pedigrees. We obtained experiment-wide significant linkage on chromosome 7q34 (LOD score 3.53, P < 0.001), substantially stronger than that observed in the genome-wide scan. Support for linkage was sustained on chromosomes 2p13, 4q31, 8q13, 13q32, 14q21, and 17q11, though at a more modest level. Family-based association analysis was consistent with the linkage results at all regions with linkage evidence, except 4q an 8q, but the results fell short of statistical significance. Three of the previously implicated regions—9q31, 10q21 and 10q24—showed substantial reduction in evidence of linkage. Our results strongly support 7q34 as a region harboring susceptibility locus for BP. Somewhat lesser, yet notable support was obtained for 2p13, 4q31, 8q13, 13q32, 14q21, and 17q11. These regions could be considered prime candidates for future gene finding efforts. © 2010 Wiley-Liss, Inc.

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