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A genome-wide search for chromosomal loci linked to bipolar affective disorder in the Old Order Amish

Nature Genetics volume 12, pages 431–435 (1996)Cite this article

Abstract

The most characteristic features of bipolar affective disorder (manic-depressive illness) are episodes of mania (bipolar I, BPI) or hypomania (bipolar II, BPII) interspersed with periods of depression. Manic-depressive illness afflicts about one percent of the population, and if untreated, is associated with an approximately 20% risk of suicide1. Twin, family and adoption studies provide compelling evidence for a partial genetic aetiology, but the mode(s) of inheritance has not been identified2. Nonetheless, the majority of genetic linkage studies have assumed classical mendelian inheritance attributable to a single major gene. Although segregation analyses have yielded inconsistent results (with most studies rejecting a single locus inheritance model), the best single gene model is dominant inheritance if only BPI is considered3. Reported linkages of bipolar affective disorder on chromosomes 11, 18, 21 and X have been difficult to substantiate, and additional studies are required for replication or exclusion of these regions4–9. We now present the results of our genome-wide linkage analyses that provide evidence that regions on chromosomes 6, 13 and 15 harbour susceptibility loci for bipolar affective disorder, suggesting that bipolar affective disorder in the Old Order Amish is inherited as a complex trait.

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Authors and Affiliations

  1. Clinical Neuroscience Branch, IRP, NIMH, NIH, Bldg. 49, Rm.BlEE16, 49 Convent Drive, MSC 4405, Bethesda, Maryland, 20892, USA

    Edward I. Ginns & Steven M. Paul

  2. Columbia University and New York State Psychiatric Institute, New York, New York, 10032, USA

    Jurg Ott & Cathy S.J. Fann

  3. Department of Psychiatry, University of Miami School of Medicine, Miami, Florida, 33136, USA

    Janice A. Egeland & Cleona R. Allen

  4. Child Study Center, Yale University School of Medicine, New Haven, Connecticut, 06520, USA

    David L. Pauls

  5. Human Genome Research Center, Evry, France

    Jean Weissenbach

  6. Genome Therapeutics Corporation, Waltham, Massachusetts, 02154, USA

    John P. Carulli, Kathleen M. Falls & Tim P. Keith

  7. Lilly Research Laboratories, Eli Lilly and Co., and Departments of Psychiatry, Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, 46285, USA

    Steven M. Paul

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Ginns, E., Ott, J., Egeland, J. et al. A genome-wide search for chromosomal loci linked to bipolar affective disorder in the Old Order Amish. Nat Genet 12, 431–435 (1996). https://doi.org/10.1038/ng0496-431

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