Parent-of-origin effect in the segregation analysis of bipolar affective disorder families

Abstract

The purpose of this study is to test for heterogeneity in bipolar families based on the differential parental transmission of disease. Complex segregation analyses of 260 bipolar families, ascertained by the Johns Hopkins Bipolar Disorder Study, was performed based on the evidence for a parent-of-origin effect in the inheritance pattern by using REGD in Statistical Analysis for Genetic Epidemiology, Release 3.1 program. A Mendelian dominant model provided the best explanation in 57 paternal pedigrees (pedigrees with an affected paternal lineage). No evidence of Mendelian inheritance existed among 141 pedigrees showing maternal transmission. A likelihood ratio test for heterogeneity on the basis of best-fitting Mendelian dominant model showed significant differences between these two groups. These results suggest that pedigrees with no evidence of maternal transmission of bipolar disorder may represent a unique genetic subgroup of multiplex bipolar families.