Bipolar disorder: Evidence for a major locus
Article first published online: 3 JUN 2005
Copyright © 1995 Wiley-Liss, Inc., A Wiley Company
American Journal of Medical Genetics
Volume 60, Issue 5, pages 370–376, 9 October 1995
How to Cite
Spence, M. A., Flodman, P. L., Sadovnick, A. D., Bailey-Wilson, J. E., Ameli, H. and Remick, R. A. (1995), Bipolar disorder: Evidence for a major locus. Am. J. Med. Genet., 60: 370–376. doi: 10.1002/ajmg.1320600505
- Issue published online: 3 JUN 2005
- Article first published online: 3 JUN 2005
- Manuscript Revised: 23 JAN 1995
- Manuscript Received: 24 MAR 1994
- bipolar disorders;
- segregation analysis;
- major gene;
- family study
Complex segregation analyses were conducted on families of bipolar I and bipolar II probands to delineate the mode of inheritance. The probands were ascertained from consecutive referrals to the Mood Disorder Service, University Hospital, University of British Columbia and diagnosed by DSM-III-R and Research Diagnostic Criteria. Data were available on over 1,500 first-degree relatives of the 186 Caucasian probands.
The purpose of the analyses was to determine if, after correcting for age and birth cohort, there was evidence for a single major locus. Five models were fit to the data using the statistical package SAGE: (i) dominant, (ii) recessive, (iii) arbitrary mendelian inheritance, (iv) environmental, and (v) no major effects.
A single dominant, mendelian major locus was the best fitting of these models for the sample of bipolar I and II probands when only bipolar relatives were defined as affected (polygenic inheritance could not be tested). Adding recurrent major depression to the diagnosis “affected” for relatives reduced the evidence for a major locus effect. Our findings support the undertaking of linkage studies and are consistent with the analyses of the National Institutes of Mental Health (NIMH) Collaborative Study data by Rice et al. (Arch Gen Psychiatry 44: 441–447, 1987) and Blangero and Elston (Genet Epidemiol 6:221–227, 1989). © 1995 Wiley-Liss, Inc.