Suggestive evidence of a locus on chromosome 10p using the NIMH genetics initiative bipolar affective disorder pedigrees

As part of a four-center NIMH Genetics Initiative on Bipolar Disorder, a ge nome screen using 365 markers was performed on 540 DNAs from 97 families, e nriched for affected relative pairs. This is the largest uniformly ascertai ned and assessed linkage sample for this disease, and includes 232 subjects diagnosed with bipolar I (BPI), 32 with schizo-affective, bipolar type (SA BP), 72 with bipolar II (DPD), and 88 with unipolar recurrent depression (U PR). A hierarchical set of definitions of affected status was examined. Und er Model I, affected individuals were those with a diagnosis of BPI or SABP , Model PI included as affected those fitting Model I plus BPII, and Model LII included those fitting Model II plus UPR. This data set was previously analyzed using primarily affected sib pair methods. We report the results o f nonparametric linkage analyses of the extended pedigree structure using t he program Genehunter Plus. The strongest finding was a lod score of 2.5 ob tained on chromosome 10 near the marker D10S1423 with diagnosis as defined under Model II, This region has been previously implicated in genome-wide s tudies of schizophrenia and bipolar disorder. Other chromosomal regions wit h lod scores over 1.50 for at least one Model Included chromosomes 8 (Model III), 16 (Model III), and 20 (Model I). Am. J. Med. Genet. (Neuropsychiatr , Genet.) 96:18-23, 2000 (C) 2000 Wiley-Liss, Inc.