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

OBJECTIVE: The purpose of this study is to test for heterogeneity in bipolar families based on the differential parental transmission of disease. METHODS: 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. RESULTS: 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. CONCLUSION: These results suggest that pedigrees with no evidence of maternal transmission of bipolar disorder may represent a unique genetic subgroup of multiplex bipolar families.