A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26.

Bipolar affective disorder is a heritable, relatively common, severe mood disorder with lifetime prevalence up to 4%. We report the results of a genome-wide linkage analysis conducted on a cohort of 35 Australian bipolar disorder families which identified evidence of significant linkage on chromosome 15q25-26 and suggestive evidence of linkage on chromosomes 4q, 6q and 13q. Subsequent fine-mapping of the chromosome 15q markers, using allele frequencies calculated from our cohort, gave significant results with a maximum two-point LOD score of 3.38 and multipoint LOD score of 4.58 for marker D15S130. Haplotype analysis based on pedigree-specific, identical-by-descent allele sharing, supported the location of a bipolar susceptibility gene within the Z(max-1) linkage confidence interval of 17 cM, or 6.2 Mb, between markers D15S979 and D15S816. Non-parametric and affecteds-only linkage analysis further verified the linkage signal in this region. A maximum NPL score of 3.38 (P=0.0008) obtained at 107.16 cM (near D15S130), and a maximum two-point LOD score of 2.97 obtained at marker D15S1004 (affecteds only), support the original genome-wide findings on chromosome 15q. These results are consistent with four independent positive linkage studies of mood and psychotic disorders, and raise the possibility that a common gene for susceptibility to bipolar disorder, and other psychiatric disorders may lie in this chromosome 15q25-26 region.

Implications of genetic risk information in families with a high density of bipolar disorder: an exploratory study.

While major susceptibility genes for bipolar disorder are yet to be identified, the opportunity exists to systematically ascertain the important issues and societal implications of genetic risk determination for bipolar disorder prior to these technological advances becoming widely available. This study explores, in a sample of families with a high density of bipolar disorder: (i) attitudes to predictive genetic and prenatal testing, using different risk frames; (ii) attributions for bipolar disorder, in particular the degree to which a genetic model is endorsed; and (iii) the impact of these attributions on the perceived stigma of bipolar disorder. A qualitative methodology was selected as most appropriate as no previous research has examined this issue. Participants were ascertained through a molecular genetics study of bipolar disorder. In-depth interviews were conducted with 21 members of families with a high density of bipolar disorder. Most participants reported being interested in genetic testing if it gave a definitive answer, while expressed interest in testing was lower if it gave a probable answer only. Almost all stressed that a genetic susceptibility and environmental factors interacted. Most participants felt that a genetic explanation was likely to decrease the stigma associated with bipolar disorder as it shifted the locus of control and responsibility away from the individual towards the role of heredity. Findings indicate that expressed interest in genetic testing depends on the certainty imparted by the test. Results suggest that families with bipolar disorder are likely to benefit psychologically from information about the genetic basis of bipolar disorder.