Sibs affected with BPII are more likely than sibs with BPI to share the linked region on chromosome 18q21

We have suggested that bipolar II disorder (BPII) might be genetically less complex than bipolar I (BPI). Our previous study of 28 families ascertained through BPI probands also revealed that sibs affected with BPII were more likely than other affected sib pairs to share paternally-transmitted alleles of markers on chromosome 18q21. We now confirm this finding using haplotype data and test the finding prospectively in a new sample of 30 families. Subjects were interviewed by a psychiatrist and diagnosed according to RDC. The diagnosis of BPII required recurrent major depression as well as hypomania, and showed good reliability in our hands (inter-rater k = 0.71). Genotypes from 32 markers on 18q were assembled into haplotypes by GENEHUNTER. Affected sib pairs were scored fpr unambiguous sharing of paternal haplotypes between D18S64 and D18S1134, site of the strongest linkage in our previous analyses. In the original sample (n = 243), only pairs in which both sibs were diagnosed with BPII showed significant haplotype sharing (18 sharing vs. 4 nonsharing, P = 0.003), while BPI-BPI sib pairs did not. Similar results were seen in the new sample (n = 259). Again, only pairs in which both sibs were diagnosed with BPII showed significant haplotype sharing (9 sharing vs. 2 nonsharing, P = 0.035). These findings, although limited by the small numbers of BPII-BPII sib pairs, demonstrate in two independent samples that sibs affected with BPII are more likely than sibs with BPI to share the linked region on chromosome 18q21.