与自闭症相关的遗传变异的表型效应
Thomas Rolland1, Freddy Cliquet2, Richard J L Anney3
1Human Genetics and Cognitive Functions, Institut Pasteur, UMR3571 CNRS, IUF, Université Paris Cité, Paris, France. thomas.rolland@pasteur.fr.
Nature medicine
|June 26, 2023
概括
自闭症相关基因中的罕见功能丧失变异与智力和社会经济地位的降低有关,即使在没有自闭症诊断的个体中也是如此. 这些遗传影响超出了自闭症谱系障碍的诊断标准.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 社会学 社会学 社会学
背景情况:
- 超过100个基因与自闭症有关,但它们在未被诊断的个体中的患病率和影响尚不清楚.
- 除了正式的自闭症诊断外,表型多样性还需要进一步调查.
- 特定基因中的功能丧失 (LoF) 变体与神经发育条件有关.
研究的目的:
- 在被诊断和未被诊断的个体中调查自闭症相关基因中罕见的LoF变异的流行率和表型相关物.
- 探索这些变异与社会人口统计学因素和认知能力的关联.
- 为了检查LoF变异载体中的大脑解剖学差异.
主要方法:
- 分析了来自13000多名自闭症患者和21万未被诊断患者的遗传数据.
- 185个自闭症基因和2,492个LoF不耐受基因中与LoF变异相关的自闭症概率比率的估计.
- 认知和社会人口因素的评估,包括流体智力,资格水平,收入和物质剥夺.
- 对21040名英国生物库参与者的脑成像数据的检查.
主要成果:
- 自闭症相关基因中的LoF变异与流体智力,资格水平和收入的显著下降以及物质剥夺的增加有关,即使在未被诊断的个体中也是如此.
- 与其他LoF不耐受基因相比,这些影响在与自闭症相关的基因中更加明显.
- 在LoF携带者和非携带者之间检测到的整体大脑解剖学没有显著差异.
结论:
- 这项研究强调了检查遗传变异效应的重要性,超出了自闭症等分类诊断的范围.
- 不管自闭症的诊断如何,LoF变体对社会人口统计学因素和认知能力都有可衡量的影响.
- 需要进一步的研究来了解这些遗传变异和社会人口统计结果之间的复杂关联,以改善对受影响个体的支持.
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