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

被引：0
作者：
Savitz J. [1 ]
Van Der Merwe L. [2 ]
Solms M. [3 ]
Ramesar R. [1 ]
机构：
[1] Division of Human Genetics, Institute for Infectious Disease and Molecular Medicine, University of Cape Town
[2] Biostatistics Unit, Medical Research Council of South Africa
[3] Departments of Psychology and Neurology, University of Cape Town
来源：
NeuroMolecular Medicine | 2007年 / 9卷 / 2期
关键词：
Bipolar disorder; Cognition; Endophenotype; Gene; Memory;
D O I：
10.1007/BF02685885
中图分类号：
学科分类号：
摘要：
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. Copyright © 2007 Humana Press Inc. All rights of any nature whatsoever reserved.
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页码：101 / 116
页数：15
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