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

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Abstract

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. A focused 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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  1. Division of Human Genetics, Institute for Infectious Disease and Molecular Medicine, University of Cape Town, South Africa

    Jonathan Savitz & Rajkumar Ramesar

  2. Biostatistics Unit, Medical Research Council of South Africa, South Africa

    Lize van der Merwe

  3. Departments of Psychology and Neurology, University of Cape Town, South Africa

    Mark Solms

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  1. Jonathan Savitz
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Savitz, J., van der Merwe, L., Solms, M. et al. A linkage and family-based association analysis of a potential neurocognitive endophenotype of bipolar disorder. Neuromol Med 9, 101–116 (2007). https://doi.org/10.1007/BF02685885

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