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Genome-wide scan of bipolar disorder in 65 pedigrees: supportive evidence for linkage at 8q24, 18q22, 4q32, 2p12, and 13q12

Molecular Psychiatry volume 8, pages 288–298 (2003)Cite this article

Abstract

The purpose of this study was to assess 65 pedigrees ascertained through a Bipolar I (BPI) proband for evidence of linkage, using nonparametric methods in a genome-wide scan and for possible parent of origin effect using several analytical methods. We identified 15 loci with nominally significant evidence for increased allele sharing among affected relative pairs. Eight of these regions, at 8q24, 18q22, 4q32, 13q12, 4q35, 10q26, 2p12, and 12q24, directly overlap with previously reported evidence of linkage to bipolar disorder. Five regions at 20p13, 2p22, 14q23, 9p13, and 1q41 are within several Mb of previously reported regions. We report our findings in rank order and the top five markers had an NPL>2.5. The peak finding in these regions were D8S256 at 8q24, NPL 3.13; D18S878 at 18q22, NPL 2.90; D4S1629 at 4q32, NPL 2.80; D2S99 at 2p12, NPL 2.54; and D13S1493 at 13q12, NPL 2.53. No locus produced statistically significant evidence for linkage at the genome-wide level. The parent of origin effect was studied and consistent with our previous findings, evidence for a locus on 18q22 was predominantly from families wherein the father or paternal lineage was affected. There was evidence consistent with paternal imprinting at the loci on 13q12 and 1q41.

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Acknowledgements

This work was supported by NIMH research Grants RO1-MH-42243 (Dr DePaulo) and K20-MH-01088 (Dr McInnis), the Charles A Dana foundation, the National Alliance for Research on Schizophrenia and Depression, The Stanley Medical Research Institute (Dr DePaulo), the Alexander Wilson Schweizer Fund, the Affective Disorders Fund, and the George Browne Laboratory Fund. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to the Johns Hopkins University, Contract Number N01-HG 65403. We are grateful to the probands and family members for their participation in this study. We appreciate the efforts of research support staff and volunteers and their contribution to the success of our work. We thank Barbara W Schweizer BS, RN, for co-coordinating our ascertainment efforts, as well as being a compassionate resource to the participating families in times of need.

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Author notes

  1. F J McMahon

    Present address: NIMH, 36 Convent Dr. Rm 4C08 MSC 4095, Bethesda, MD, 20892, USA

  2. C Friddle

    Present address: Lexicon Genetics Inc., The Woodlands, TX, USA

  3. O Colin Stine

    Present address: University of Maryland, Baltimore, MD, USA

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA

    M G McInnis, V L Willour, F J McMahon, S G Simpson, A M Addington, D F MacKinnon, J B Potash, A T Mahoney, J Chellis, Y Huo, T Swift-Scanlan, H Chen, R Koskela, O Colin Stine, K R Jamison, P Zandi & J Raymond DePaulo

  2. Department of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, USA

    M G McInnis, T-H Lan, T H Beaty & P Zandi

  3. Department of Psychiatry, Yu-Li Veterans Hospital, Taipei, Taiwan

    T-H Lan

  4. Institute of Genetics, School of Life Science, National Yang-Ming University, Hualien, Taiwan

    T-H Lan

  5. MRC Biostatistics Unit, Cambridge, UK

    P Holmans

  6. Department of Psychiatry, Tufts University, Boston, MA

    S E Folstein & D Botstein

  7. Department of Genetics, Stanford University, Palo Alto, CA, USA

    K Ranade & C Friddle

  8. CNS Genetics Corp, Saginaw, 48603, MI, USA

    T Marr

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McInnis, M., Lan, TH., Willour, V. et al. Genome-wide scan of bipolar disorder in 65 pedigrees: supportive evidence for linkage at 8q24, 18q22, 4q32, 2p12, and 13q12. Mol Psychiatry 8, 288–298 (2003). https://doi.org/10.1038/sj.mp.4001277

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  • DOI: https://doi.org/10.1038/sj.mp.4001277

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