Nature Genetics
12, 431 - 435 (1996)
doi:10.1038/ng0496-431
A genome-wide search for chromosomal loci linked to bipolar affective disorder in the Old Order AmishEdward I. Ginns1, 8, Jurg Ott2, Janice A. Egeland3, Cleona R. Allen3, Cathy S.J. Fann2, David L. Pauls4, Jean Weissenbach5, John P. Carulli6, Kathleen M. Falls6, Tim P. Keith6
& Steven M. Paul1, 7
1Clinical Neuroscience Branch, IRP, NIMH, NIH, Bldg. 49, Rm.BlEE16, 49 Convent Drive, MSC 4405, Bethesda, Maryland 20892, USA.
2Columbia University and New York State Psychiatric Institute, New York, New York 10032, USA.
3Department of Psychiatry, University of Miami School of Medicine, Miami, Florida 33136, USA.
4Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
5Human Genome Research Center, Evry, France.
6Genome Therapeutics Corporation, Waltham, Massachusetts 02154, USA.
7Lilly Research Laboratories, Eli Lilly and Co., and Departments of Psychiatry, Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46285, USA.
8Correspondence should be addressed to E.I.G. 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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