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Keywords:

  • bipolar disorder;
  • bipolar II disorder;
  • genehunter-chromosomes;
  • genome-wide scan;
  • non-parametric analysis;
  • phenotype

Objective:  Bipolar disorder (BD) II is characterized by recurrent hypomanic and depressive episodes and has been somewhat of a controversial diagnosis since its description in the 1970s. Clinical opinions notwithstanding, the biological validity of BD II was supported in a genetic study of 58 multiplex bipolar families wherein the statistical evidence for linkage derived from BD II sibling-pairs sharing marker alleles on chromosome 18q. The BD II phenotype alone has never been studied in a genome-wide scan analysis in the current or other bipolar family samples. We have performed genome-wide non-parametric analysis on 74 bipolar pedigrees using only the BD II phenotype as affection model.

Methods:  This sample consists of the 65 pedigrees previously reported and 9 additional novel pedigrees that had BD II exclusively, as the affected phenotype. In the entire sample, there were 146 all possible relative-pairs. Analysis was performed using the non-parametric method in GENEHUNTER, with the ‘ALL’ option that computes linkage scores in all individuals in a pedigree simultaneously.

Results:  The current analyses supported the previous finding on chromosome 18q21. In addition a peak with a non-parametric LOD (NPL) of 2.07 occurred between D9S915 and D9S2157, located on 9q34. Analysis of the nine BD II families alone identified peaks on 9p13 and 9q33, with NPL scores of 3.20 and 2.09, respectively. There was no evidence at 18q21 in these nine families.

Conclusions:  This suggests that there may be substantial differences in the etiology of BD in families that have BD II exclusively as the diagnosis.