近日，瑞士洛桑大学Zoltán Kutalik及其小组的研究开发出了亲本对236781个个体复杂性状的影响。相关论文于2025年8月6日发表在《自然》杂志上。

在这里，课题组研究人员提出了一种方法来推断没有亲本基因组的等位基因的起源，利用染色体间相位，线粒体和X染色体数据，以及兄弟姐妹中的性别特异性交叉。应用于英国生物银行，这使得多达109385个人的父母血统推断成为可能。全基因组关联研究扫描了59个复杂性状和14000多个蛋白质数量性状位点，对比了母系和父系的影响，确定了30多个POEs，并确认了50%以上的已知关联。超过三分之一的人表现出相反的父母影响，特别是在与生长有关的特征（例如，IGF1和身高）和代谢（例如，2型糖尿病和甘油三酯水平）。来自爱沙尼亚生物银行的85050名个体和来自挪威母亲，父亲和儿童队列研究（MoBa）的42346名后代的复制验证了87%的可测试关联。总的来说，他们的发现强调了POE对复杂特征的贡献，并支持了父母冲突假说，为这一尚未得到充分研究的进化现象提供了令人信服的证据。

据了解，当一个遗传变异的影响取决于它的亲本来源时，就会发生亲本效应。传统上认为，遗传变异与基因组印记有关，它被认为是由于父母在将抗性分配给后代的问题上发生冲突，从而导致父母对后代的相反影响。尽管它们很重要，但由于缺乏亲本基因组，POEs在复杂性状中的研究仍然不足。

附：英文原文

Title: Parent-of-origin effects on complex traits in up to 236,781 individuals

Author: Hofmeister, Robin J., Cavinato, Tho, Karimi, Roya, van der Graaf, Adriaan, Pajuste, Fanny-Dhelia, Kronberg, Jaanika, Taba, Nele, Mgi, Reedik, Vaudel, Marc, Rubinacci, Simone, Johansson, Stefan, Milani, Lili, Delaneau, Olivier, Kutalik, Zoltn

Issue&Volume: 2025-08-06

Abstract: Parent-of-origin effects (POEs) occur when the effect of a genetic variant depends on its parental origin1. Traditionally linked to genomic imprinting, POEs are believed to occur due to parental conflict over resource allocation to offspring, resulting in opposing parental influences2. Despite their importance, POEs remain underexplored in complex traits, owing to the lack of parental genomes. Here we present an approach to infer the parent of origin of alleles without parental genomes, leveraging interchromosomal phasing, mitochondrial and X chromosome data, and sex-specific crossover in siblings. Applied to the UK Biobank, this enabled parent-of-origin inference for up to 109,385 individuals. Genome-wide association study scans for 59 complex traits and over 14,000 protein quantitative trait loci contrasting maternal and paternal effects identified over 30 POEs and confirmed more than 50% of known associations. More than one third of these showed opposite parental influences, especially for traits related to growth (for example, IGF1 and height) and metabolism (for example, type 2 diabetes and triglyceride levels). Replication in up to 85,050 individuals from the Estonian Biobank and 42,346 offspring from the Norwegian Mother, Father and Child Cohort Study (MoBa) validated 87% of testable associations. Overall, our findings highlight the contribution of POEs to complex traits and support the parental conflict hypothesis, providing compelling evidence for this understudied evolutionary phenomenon.

DOI: 10.1038/s41586-025-09357-5

Source: https://www.nature.com/articles/s41586-025-09357-5