Implication of the APP Gene in Intellectual Abilities.
Implication of the APP Gene in Intellectual Abilities.
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DOI：
10.3233/jad-170049
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Zayats T
中科院分区：
文献类型：
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作者：
Myrum C;Nikolaienko O;Bramham CR;Haavik J;Zayats T
认知功能是高度可遗传和多基因的，尽管这种遗传影响的来源尚不清楚。在神经生物学水平上，这些功能依赖于有效的神经可塑性，其中活性调节细胞骨架相关蛋白(ARC)起着至关重要的作用。鉴于ARC在大脑可塑性和记忆形成中的关键作用，研究ARC基因复合体是否可能对智力功能的遗传成分做出贡献。Avon亲子纵向研究(ALSPAC，N = 5,165)测试了ARC复合体与儿童智商(IQ)的关系。由于阿尔茨海默病(AD)的基因与认知功能相同，因此对AD样本(17,008例，37,154名对照)进行了跟踪调查。在ALSPAC中，ARC复合体与言语智商和总智商(经验p = 分别为0.027和0.041)有关。在AD样本中证实了APP基因中最强的单一变异信号(rs2830077；经验性p = 0.018)(p = 2.76E-03)。对该变异体的功能分析表明，该变异体优先结合转录因子CP2。这项研究表明APP与儿童智商有关。虽然还需要后续研究，但这一观察结果可能有助于阐明与认知功能障碍相关的疾病的病因，如阿尔茨海默病。
Cognitive functions are highly heritable and polygenic, though the source of this genetic influence is unclear. On the neurobiological level, these functions rely on effective neuroplasticity, in which the activity-regulated cytoskeleton associated protein (ARC) plays an essential role. To examine whether the ARC gene complex may contribute to the genetic components of intellectual function given the crucial role of ARC in brain plasticity and memory formation. The ARC complex was tested for association with intelligence (IQ) in children from the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 5,165). As Alzheimer’s disease (AD) shares genetics with cognitive functioning, the association was followed up in an AD sample (17,008 cases, 37,154 controls). The ARC complex revealed association with verbal and total IQ (empirical p = 0.027 and 0.041, respectively) in the ALSPAC. The strongest single variant signal (rs2830077; empirical p = 0.018), within the APP gene, was confirmed in the AD sample (p = 2.76E-03). Functional analyses of this variant showed its preferential binding to the transcription factor CP2. This study implicates APP in childhood IQ. While follow-up studies are needed, this observation could help elucidate the etiology of disorders associated with cognitive dysfunction, such as AD.