Genetic linkage to chromosome 4q35 in bipolar affective disorder

P. R. Schofield, L. J. Adams, R. Badenhop, M. Moses, S. L. Fielder, A. Rosso, J. A. Donald, P. B. Mitchell

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Bipolar affective disorder is characterised by severe mood swings (mania and depression) and affects 1-2% of the population. Its complex genetic nature, variable age of onset, and age-specific penetrance confounds linkage studies. No predisposing genes have been identified although a number of groups have mapped susceptibility loci with linkage having been reported to several chromosomes. We have undertaken a two-stage genome screen using 214 microsatellite markers on 87 individuals from the most powerful pedigree in our cohort. The data were analysed by two-point linkage analysis and nonparametric methods under several diagnostic models. Initial lod scores greater than 2 were obtained for four markers although after completion of the second stage, only one marker D4S1652 (θ = 0.15) remained with a lod score of 2.2. Multipoint analysis using additional markers gave a maximum lod score of z = 3.19 between D4S408 and D4S2924. Nonparametric analyses supported our conclusions with a maximum score of 2.61 (P = 0.01) between D4S1652 and D4S171 using Genehunter. Initial analysis of a further 10 pedigrees indicates the presence of the 4q35 locus in at least one additional pedigree. A high density, 1-2 cM map is being constructed using 25 pedigrees (491 individuals, including 115 affected members) to establish a minimal disease haplotype. In summary, our results suggest the presence of an additional susceptibility locus for bipolar disorder on chromosome 4q35.

Original languageEnglish
Pages (from-to)474-475
Number of pages2
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume81
Issue number6
Publication statusPublished - 6 Nov 1998

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