芬兰分离物的外因组测序增强了罕见变异的结合力
Adam E Locke1,2,3, Karyn Meltz Steinberg2,4, Charleston W K Chiang5,6,7
1Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Nature
|August 2, 2019
概括
芬兰外基因组测序发现了26个新的有害基因对定量心脏代谢特征,其中19个是芬兰人群特有的. 这突显了孤立群体在遗传研究中的力量.
科学领域:
- 遗传学和基因组学
- 心血管和新陈代谢疾病
背景情况:
- 外基因组测序研究往往没有能力检测影响复杂特征的罕见,大效应的等位基因.
- 由于其独特的人口历史,孤立的群体,如芬兰北部/东部群体,具有更高的有害基因频率.
研究的目的:
- 在芬兰队列中使用外基因组测序来研究罕见编码变异在定量心脏代谢特征中的作用.
- 识别新的有害基因并评估其在芬兰人口中的频率和分布.
主要方法:
- 对来自芬兰北部和东部近2万个人的64种定量心脏代谢特征进行了外基因组范围的关联研究.
- 与其他欧洲人群相比,分析了已识别的有害基因的频率和地理分布.
主要成果:
- 在64个定量特征中确定了26个新关联的有害基因.
- 其中19个基因基因在芬兰人群中具有显著的丰富性 (超过20倍的频率),并且表现出地理集群.
- 这些发现表明,芬兰人群的隔离对发现影响复杂特征的罕见变异具有强大作用.
结论:
- 芬兰人口独特的遗传历史有助于识别影响心脏代谢特征的罕见有害基因.
- 与更广泛,更多样化的群体相比,孤立群体中的外因组测序为变体发现提供了更大的统计能力.
- 在类似的隔离物中进行的未来遗传研究可能会对复杂疾病遗传学产生重大见解.
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