The NIMH sponsored genetics initiative has ascertained a total of 153 multiplex bipolar pedigrees. These pedigrees have been genotyped in two sets of 97 and 56 pedigree; analyses were performed under three models of affection: Model 1: bipolar I (BPI) and schizoaffectivemanic (SABP); Model 2: add bipolar II (BPII); and Model 3: add recurrent major depression (UPR). The first set (97 pedigrees) contains 232 BPI, 32 SABP, 72 BPII, and 88 UPR subjects; the second set contains 144 BPI, 43 BPII, 44 UPR, and 4 SABP subjects. We have genotyped 61 highly polymorphic markers on chromosomes 2,11,13, and 14 in the second set in addition to 42 markers genotyped in the first set of 97 pedigrees. In the first set, analyses using SIBPAL identified six loci on chromosomes 2,11,13, and 14 with a P value < 0.05. SIBPAL analysis of the second set of 56 pedigrees identified seven loci with a P value < 0.05. None of the initial findings in the first set was not replicated in the second set of pedigrees. In the second set, there was sug-gestive evidence (SIBPAL) of a susceptibility locus at adjacent loci D11S1948 (P = 0.0098) and D11S2362 (P = 0.0055) under Model 2. The GENEHUNTER results were: NPL= 2.4 (P = 0.006) and HLOD = 2.58 (alpha = 0.37) at D11S1984. Re-analysis of the data in the initial set of 97 pedigrees identified increased allele sharing at D11S2362 with a P value of 0.02 (Model 3). These data reawaken the question of a susceptibility locus on chromosome 11p.
|Number of pages||1|
|Journal||American Journal of Medical Genetics - Neuropsychiatric Genetics|
|State||Published - Nov 6 1998|