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至少有26个晚发性阿尔茨海默病 (LOAD) 风险位置显示最近的进化选择. 这些发现表明,LOAD病因和治疗策略可能需要根据不同的祖先种群量身定制.

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科学领域:

  • 遗传学 是一个遗传学.
  • 进化生物学 进化生物学
  • 神经科学是一个神经科学.

背景情况:

  • 超过70个单核酸多态 (SNP) 与晚发性阿尔茨海默病 (LOAD) 有关.
  • 常见的LOAD风险等位基因可能会在生命早期带来好处,推动自然选择在不同种群中存在差异.
  • 调查跨祖先的LOAD风险变异中的选择可以阐明特定人群的疾病病因.

研究的目的:

  • 为了测试26个全球人口中LOAD风险位点的近期进化选择.
  • 识别在不同祖先群体中选择中的LOAD风险变异,以了解特定群体的LOAD病因学.
  • 为了确定是否选择模式在祖先之间有所不同,这意味着共患病,干预疗效和非目标效应的变化.

主要方法:

  • 利用了来自1000个基因组项目的2,504名参与者的全基因组序列数据.
  • 采用Selscan计算全基因组的nSL得分,用于26个群体最近的进化选择.
  • 识别了前1%的nSL存储点在LOAD相关基因附近,并使用ADSP控制数据验证了这些发现.

主要成果:

  • 在75个LOAD位点中,52个显示在前1%的变异,至少在两个人群中存在变异.
  • 其中26个位点在相应的种族/民族 (R/E) 群体中使用ADSP数据进行了验证.
  • 在22个种群中选择了ICA1并对大多数ADSP R/E组进行了验证;途径分析揭示了不同的生物过程,例如非洲人的微管功能选择.

结论:

  • 至少有26个LOAD风险位表现出最近进化选择的证据.
  • 路径分析表明,在不同的超级群体中,不同的生物功能正在选择中.
  • LOAD病因学,并发病和前发病模式可能因超级人口而异,需要定制的研究和干预措施.