牛津大学Loic Yengo研究组揭示了配子相不平衡对复杂性状遗传力的贡献。2025年5月19日，国际知名学术期刊《自然—遗传学》发表了这一成果。

在这里，该课题组引入了基于不平衡基因组的限制最大似然（DGREML）方法，以同时量化SNPs对遗传力的加性贡献及其方向协方差。课题组研究人员将DGREML应用于来自不同生物库的55万个体的26种表型，发现交叉常染色体GPD对身高、受教育程度、智力、收入、自评价健康状况和久坐行为的SNPs遗传力贡献了10-27%。该课题组人员观察到GPD对英国、中国和日本人群身高遗传力的差异贡献。最后，受教育程度和身高的双变量DGREML分析表明，跨常染色体GPD至少贡献了32%的遗传相关性。总之，他们的多功能和强大的方法揭示了复杂性状的遗传结构的未被研究的特征，并告知产生这些特征的潜在机制。

据悉，非随机交配诱导非连锁遗传变异之间的全基因组相关性，称为配子相不平衡（GPD），其对遗传力的贡献尚未确定。

附：英文原文

Title: The contribution of gametic phase disequilibrium to the heritability of complex traits

Author: Zhang, Yuanxiang, Sakaue, Saori, Morris, Sam, Graff, Mariaelisa, Yamamoto, Kenichi, Chen, Zhengming, Li, Liming, Keller, Matthew C., Goddard, Michael E., Walters, Robin G., Okada, Yukinori, Visscher, Peter M., Yengo, Loic

Issue&Volume: 2025-05-19

Abstract: Nonrandom mating induces genome-wide correlations between unlinked genetic variants, known as gametic phase disequilibrium (GPD), whose contribution to heritability remains uncharacterized. Here we introduce the disequilibrium genome-based restricted maximum likelihood (DGREML) method to simultaneously quantify the additive contribution of SNPs to heritability and that of their directional covariances. We applied DGREML to 26 phenotypes of 550,000 individuals from diverse biobanks and found that cross-autosome GPD contributes 10–27% of the SNP-based heritability of height, educational attainment, intelligence, income, self-rated health status and sedentary behaviors. We observed a differential contribution of GPD to the heritability of height between the UK, Chinese and Japanese populations. Finally, bivariate DGREML analyses of educational attainment and height show that cross-autosome GPD contributes at least 32% of their genetic correlation. Altogether, our versatile and powerful method reveals understudied features of the genetic architecture of complex traits and informs potential mechanisms generating these features.

DOI: 10.1038/s41588-025-02192-4

Source: https://www.nature.com/articles/s41588-025-02192-4