中国科学院上海营养与健康研究所Sijia Wang、Andrew E. Teschendorff和中国科学院北京基因组研究所Fan Liu课题组合作，利用东亚人血液甲基化数量性状位点（mQTLs）分析，揭示了祖先特异性对复杂性状的影响。相关论文发表在2024年4月19日出版的《自然—遗传学》杂志上。

据悉，mQTLs对于了解DNA甲基化变化在遗传易感性中的作用至关重要，但这些位点在东亚人（EAs）中尚未得到充分表征。

研究人员从3523名中国人的全血中发现了mQTL，并在包涵1858名中国人的两个队列中进行了重现。超过9%的mQTLs具有EAs特异性，从而促进了EA特异性遗传关联的精细图谱绘制，如身高相关变异。跨mQTL热点揭示了有助于EA特异性遗传关联的生物通路，包括ERG介导的233个跨mCpG网络，该网络与造血细胞分化有关，可能反映了与ERG蛋白复合物结合效率有关的调控。9

0%以上的mQTLs在不同血细胞系之间共有，小部分血细胞系特异性mQTLs在各自血细胞系中显示出低甲基化。该研究为了解跨遗传祖先的mQTL景观，及其对细胞活动和疾病/特征的下游影响提供了新的视角。

附：英文原文

Title: Analysis of blood methylation quantitative trait loci in East Asians reveals ancestry-specific impacts on complex traits

Author: Peng, Qianqian, Liu, Xinxuan, Li, Wenran, Jing, Han, Li, Jiarui, Gao, Xingjian, Luo, Qi, Breeze, Charles E., Pan, Siyu, Zheng, Qiwen, Li, Guochao, Qian, Jiaqiang, Yuan, Liyun, Yuan, Na, You, Chenglong, Du, Siyuan, Zheng, Yuanting, Yuan, Ziyu, Tan, Jingze, Jia, Peilin, Wang, Jiucun, Zhang, Guoqing, Lu, Xianping, Shi, Leming, Guo, Shicheng, Liu, Yun, Ni, Ting, Wen, Bo, Zeng, Changqing, Jin, Li, Teschendorff, Andrew E., Liu, Fan, Wang, Sijia

Issue&Volume: 2024-04-19

Abstract: Methylation quantitative trait loci (mQTLs) are essential for understanding the role of DNA methylation changes in genetic predisposition, yet they have not been fully characterized in East Asians (EAs). Here we identified mQTLs in whole blood from 3,523 Chinese individuals and replicated them in additional 1,858 Chinese individuals from two cohorts. Over 9% of mQTLs displayed specificity to EAs, facilitating the fine-mapping of EA-specific genetic associations, as shown for variants associated with height. Trans-mQTL hotspots revealed biological pathways contributing to EA-specific genetic associations, including an ERG-mediated 233 trans-mCpG network, implicated in hematopoietic cell differentiation, which likely reflects binding efficiency modulation of the ERG protein complex. More than 90% of mQTLs were shared between different blood cell lineages, with a smaller fraction of lineage-specific mQTLs displaying preferential hypomethylation in the respective lineages. Our study provides new insights into the mQTL landscape across genetic ancestries and their downstream effects on cellular processes and diseases/traits.

DOI: 10.1038/s41588-023-01494-9

Source: https://www.nature.com/articles/s41588-023-01494-9