A linkage and family-based association analysis of a potential neurocognitive endophenotype of bipolar disorder.

Publisher: Humana Press Country of Publication: United States NLM ID: 101135365 Publication Model: Print Cited Medium: Print ISSN: 1535-1084 (Print) Linking ISSN: 15351084 NLM ISO Abbreviation: Neuromolecular Med Subsets: MEDLINE

Original Publication: Totowa, NJ : Humana Press, c2002-

Family* ; Genetic Linkage* ; Phenotype*; Bipolar Disorder/*genetics; Chromosomes, Human, Pair 22 ; Cohort Studies ; Genetic Predisposition to Disease ; Genetic Variation ; Genotype ; Humans ; Neuropsychological Tests ; Pedigree ; Quantitative Trait, Heritable ; South Africa

The identification of the genetic variants underpinning bipolar disorder (BPD) has been impeded by a complex pattern of inheritance characterized by genetic and phenotypic heterogeneity, genetic epistasis, and gene-environment interactions. In this paper two strategies were used to ameliorate these confounding factors. A unique South African sample including 190 individuals of the relatively, reproductively isolated Afrikaner population was assessed with a battery of neuropsychological tests in an attempt to identify a BPD-associated quantitative trait or endophenotype. BPD individuals performed significantly worse than their unaffected relatives on visual and verbal memory tasks, a finding congruent with the literature. Afocused linkage and family-based association study was carried out using this memory-related endophenotype. In the largest 77-strong Afrikaner pedigree significant evidence for linkage was detected on chromosome 22q11, a region previously implicated in BPD. The quantitative transmission disequilibrium tests-based association analysis suggested that functional variants of the DRD4 and MAO-A genes modulate memory-related cognition. We speculate that polymorphisms at these loci may predispose to a subtype of BPD characterized by memory-related deficits.

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Date Created: 20070714 Date Completed: 20071203 Latest Revision: 20191110

20221213

10.1007/BF02685885

17627031