COMPLEX SEGREGATION ANALYSES OF OLD ORDER AMISH FAMILIES ASCERTAINED THROUGH BIPOLAR-I INDIVIDUALS

Specific genetic hypotheses about the mode of transmission of bipolar affective disorders were examined by performing complex segregation an alyses of Old Order Amish families. The analyses were performed on 1) the total set of 42 families including 689 relatives, 2) a subset of 1 9 families consisting of those kindreds sharing common ancestors withi n three generations that contained 333 relatives, and 3) a subset of 2 3 more distantly related families with 356 relatives. When all 42 fami lies were included in the analyses, the specific mode of transmission that could be distinguished was dependent upon the diagnostic scheme u sed in the analysis. An autosomal dominant mode of inheritance could b e rejected when relatives with bipolar I, atypical bipolar, major depr essive disorder, and hypomania were included as affected, When analyse s included only the subset of families more closely related, an autoso mal dominant inheritance model was found to be consistent with transmi ssion of BP I disorder, It was not possible to distinguish between oth er transmission models with broader diagnostic schemes in this subset of families. Finally, results of analyses on the subset of more distan tly related families suggest that there is a significant proportion of Old Order Amish families in which the genetic factors contributing to the expression of bipolar illness are either polygenic or oligogenic. (C) 1995 Wiley-Liss, Inc.