Replication of suggestive linkage on chromosomes 5 and 16 in the NIMH genetics initiative bipolar pedigrees

Families who had a bipolar I (BP1) proband and at least one BP1, or schizoaffective-bipolar type (SA/BP) first-degree relative were ascertained through the NIMH Genetics Initiative. A series of hierarchical models of affection were utilized in linkage analyses. Model I considered as affected only individuals with BP1 or SA/BP; model II included all individuals in Model I as well as bipolar II individuals; and Model III included individuals diagnosed under Model II, and those with unipolar recurrent depression. An initial genome screen was completed in 540 subjects from 97 families. Genotyping at Indiana University was subsequently performed on chromosomes 3, 5, 15, 16, 17 and 22 in a replication sample of 353 individuals from 56 families. Nonparametric linkage analyses were performed using both affected sibling and relative pair methods. Analyses in the new sample on chromosome 16, with the broadest definition of affection, replicated previously reported suggestive linkage to the marker D16S2619 (lod ∼2.0). In addition, evidence of linkage was also found on chromosome 5q for models II and III (lod ∼2.5) in the same chromosomal region reported in the initial sample. Additional marker genotyping is currently underway to further delineate these linked regions.