PATTERNS OF PARENTAL TRANSMISSION AND FAMILIAL AGGREGATION MODELS IN BIPOLAR AFFECTIVE-DISORDER

Two recent studies [McMahon et al,, 1995: Am J Hum Genet 56:1277-1286; Gershon et al,, 1996: Am J Med Genet (Neuropsychiatr Genet) 67:202-20 7] reported an excess of maternal transmission in bipolar affective di sorder in multiply affected families. In a sample of 130 families asce rtained through a bipolar proband without regard to psychiatric family history we analysed the frequency of maternal (MAT) and paternal (PAT ) transmissions, the morbid risk (MR) in relatives of transmitting mot hers and fathers and the inheritance patterns in families with MAT vs. PAT transmission of the disease. In the total sample of 130 families we identified 39 families where the disease was transmitted from the p aternal side (PAT families) and 35 families where the disease was tran smitted from the maternal side (MAT families). Counting PAT and MAT tr ansmissions in these unilineal families we found nearly equal numbers for both transmission types under a narrow (BP: bipolar disorder, schi zoaffective-bipolar type disorder) and a broad definition (AFF: BP, re current unipolar depression) of the phenotype, The MRs for narrow and broad phenotypes were not significantly different in any type of PAT r elative in PAT families vs. MAT relatives in MAT families. However, in PAT families there were two times more affected females than males wi th both disease models, while in MAT families there was no MR differen ce by relatives' sex. The transmission of BP was compatible with the M endelian major gene model in PAT families and with the multifactorial model in MAT families. Extension of the relatives' phenotype led to bo rderline non-Mendelian major effects in PAT families and reproduced th e multifactorial model in MAT families. (C) 1998 Wiley-Liss, Inc.