title: A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26.
abstract: 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.
authors.affiliation: Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, NSW, Australia.
authors.forename: E Z
authors.initials: EZ
authors.lastname: McAuley
authors.forename: I P
authors.initials: IP
authors.lastname: Blair
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: J M
authors.initials: JM
authors.lastname: Fullerton
authors.forename: A
authors.initials: A
authors.lastname: Scimone
authors.forename: M
authors.initials: M
authors.lastname: Van Herten
authors.forename: M R
authors.initials: MR
authors.lastname: Evans
authors.forename: K C
authors.initials: KC
authors.lastname: Kirkby
authors.forename: J A
authors.initials: JA
authors.lastname: Donald
authors.forename: P B
authors.initials: PB
authors.lastname: Mitchell
authors.forename: P R
authors.initials: PR
authors.lastname: Schofield
mesh_terms: D000293:Adolescent; D000328:Adult; D001315:Australia; D001714:Bipolar Disorder / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D002884:Chromosomes, Human, Pair 15; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D055815:Young Adult