Genome screen of 15 Australian bipolar affective disorder pedigrees supports previously identified loci for bipolar susceptibility genes.

Objective: Despite many studies into the genetics of bipolar disorder (BP), the molecular causes underlying susceptibility to BP remain unclear. The aim of this study was to identify chromosomal regions linked to BP in a new Australian extended pedigree cohort.

Methods: We have conducted a parametric genome-wide linkage scan on 15 previously unreported Australian extended families with BP and related affective disorders, comprising 63 affected and 158 nonaffected individuals.

Positional cloning, association analysis and expression studies provide convergent evidence that the cadherin gene FAT contains a bipolar disorder susceptibility allele.

A susceptibility locus for bipolar disorder was previously localized to chromosome 4q35 by genetic linkage analysis. We have applied a positional cloning strategy, combined with association analysis and provide evidence that a cadherin gene, FAT, confers susceptibility to bipolar disorder in four independent cohorts (allelic P-values range from 0.003 to 0.

Identification, characterization, and association analysis of novel genes from the bipolar disorder susceptibility locus on chromosome 4q35.

The cause of bipolar disorder remains unknown, with little knowledge of the underlying biological, anatomical, biochemical, or genetic defect. The disorder is genetically complex, with an increasing number of loci being implicated through genetic linkage studies. We previously identified a bipolar disorder susceptibility locus on chromosome 4q35 and refined the interval harboring this susceptibility gene to approximately 5 Mb, a size that is amenable to positional cloning.

Association analysis of transcripts from the bipolar susceptibility locus on chromosome 4q35, exclusion of a pathogenic role for eight positional candidate genes.

Bipolar affective disorder is a major psychiatric illness with a population prevalence of up to 1.6%. The disorder is genetically complex.