BIPOLAR DISORDER - EVIDENCE FOR A MAJOR LOCUS

Complex segregation analyses were conducted on families of bipolar I a nd bipolar II probands to delineate the mode of inheritance. The proba nds were ascertained from consecutive referrals to the Mood Disorder S ervice, University Hospital, University of British Columbia and diagno sed by DSM-III-R and Research Diagnostic Criteria. Data were available on over 1,500 first-degree relatives of the 186 Caucasian probands. T he purpose of the analyses was to determine if, after correcting for a ge and birth cohort, there was evidence for a single major locus. Five models were fit to the data using the statistical package SAGE: i) do minant, ii) recessive, iii) arbitrary mendelian inheritance, iv) envir onmental, 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 de pression to the diagnosis ''affected'' for relatives reduced the evide nce for a major locus effect. Our findings support the undertaking of linkage studies and are consistent with the analyses of the National I nstitutes of Mental Wealth (NIMH) Collaborative Study data by Rice et al. (Arch Gen Psychiatry 44: 441-447, 1987) and Blangero and Elston (G enet Epidemiol 6:221-227, 1989). (C) 1995 Wiley-Liss, Inc.