在多达236,781个个体的复杂特征上产生父系影响
Robin J Hofmeister1,2,3,4, Théo Cavinato5,6, Roya Karimi7
1Department of Computational Biology, University of Lausanne, Lausanne, Switzerland. robin.j.hofmeister@gmail.com.
Nature
|August 6, 2025
概括
父母起源效应 (POE) 通过基于母亲或父亲遗传的差异来影响复杂的特征. 这项研究开发了一种新的方法来识别没有父母基因组的POE,揭示了它们在人类发育和新陈代谢中的重要作用.
科学领域:
- 遗传学
- 进化生物学
- 人类的复杂特征
背景情况:
- 父母起源效应 (POE) 是依赖于父母遗传的遗传影响,传统上与基因组印记和父母冲突有关.
- POE对于理解复杂的特征至关重要,但由于在没有父母基因组的情况下推断异基因起源的挑战,仍未得到充分探索.
研究的目的:
- 在不需要父母基因组的情况下开发和应用一种新的计算方法来推断等位基因的原始基因.
- 研究POE对各种复杂的人类特征和蛋白质定量特征位点 (pQTL) 的贡献.
主要方法:
- 杆性染色体间分相,线粒体和X染色体数据,以及兄弟姐妹的性别特异性交叉推断.
- 该方法应用于大型生物库 (英国生物库,爱沙尼亚生物库) 和家族队列 (MoBa) 进行全基因组关联研究 (GWAS) 和pQTL分析.
- 对比母亲和父亲的影响,以识别和验证59个复杂特征的POE.
主要成果:
- 成功推断出一个大群体 (多达109,385个) 的原始基因,并确定了30多个复杂特征和pQTL的新 POE.
- 确认了50%以上的已知关联,并发现超过三分之一的确定的POE表现出对立的母体和父体影响,特别是在生长和代谢特征方面.
- 在独立的队列中验证了87%的可测试关联,强调了研究结果的稳定性.
结论:
- 这项研究为POE推断提供了一种强大的新方法, 显著推进了复杂特征的研究.
- 这些发现突显了POE对人类表型变异的重大,但往往被忽视的贡献,支持了父母冲突假设.
- 提供了对POE作为影响人类健康和发展的重要进化现象的有力证据.
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