小柯机器人

英国布里斯托大学Josine L. Min等研究人员揭示遗传效应对DNA甲基化的影响。该项研究成果发表在2021年9月6日出版的《自然—遗传学》杂志上。

研究人员报道了对32,851名参与者进行的DNA甲基化（DNAm）定量性状位点（mQTL）分析的结果，确定了与血液中420,509个DNAm位点的DNAm相关的遗传变异。研究人员提出了一个超过27万个独立mQTL的数据库，其中8.5%包括长程（反式）关联。确定的mQTL关联解释了15-17%的DNAm的加性遗传变异。结果表明，DNAm水平的遗传结构是高度多基因的。利用远端DNAm位点之间的共享遗传控制，研究人员构建了网络，并确定了405个富含基因组注释和复杂性状的离散基因组群体。

共享的遗传变异与DNAm水平和复杂疾病都有关联，但只有在少数情况下，这些关联反映了从DNAm到性状的因果关系，或反之亦然，这表明基因型-表型图谱比以前预期的更复杂。

据悉，表征对DNAm的遗传影响提供了一个了解基因调节和疾病基础机制的机会。

附：英文原文

Title: Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

Author: Min, Josine L., Hemani, Gibran, Hannon, Eilis, Dekkers, Koen F., Castillo-Fernandez, Juan, Luijk, Ren, Carnero-Montoro, Elena, Lawson, Daniel J., Burrows, Kimberley, Suderman, Matthew, Bretherick, Andrew D., Richardson, Tom G., Klughammer, Johanna, Iotchkova, Valentina, Sharp, Gemma, Al Khleifat, Ahmad, Shatunov, Aleksey, Iacoangeli, Alfredo, McArdle, Wendy L., Ho, Karen M., Kumar, Ashish, Sderhll, Cilla, Soriano-Trraga, Carolina, Giralt-Steinhauer, Eva, Kazmi, Nabila, Mason, Dan, McRae, Allan F., Corcoran, David L., Sugden, Karen, Kasela, Silva, Cardona, Alexia, Day, Felix R., Cugliari, Giovanni, Viberti, Clara, Guarrera, Simonetta, Lerro, Michael, Gupta, Richa, Bollepalli, Sailalitha, Mandaviya, Pooja, Zeng, Yanni, Clarke, Toni-Kim, Walker, Rosie M., Schmoll, Vanessa, Czamara, Darina, Ruiz-Arenas, Carlos, Rezwan, Faisal I., Marioni, Riccardo E., Lin, Tian, Awaloff, Yvonne, Germain, Marine, Assi, Dylan, Zwamborn, Ramona, van Eijk, Kristel, Dekker, Annelot, van Dongen, Jenny, Hottenga, Jouke-Jan, Willemsen, Gonneke, Xu, Cheng-Jian, Barturen, Guillermo, Catal-Moll, Francesc, Kerick, Martin, Wang, Carol

Issue&Volume: 2021-09-06

Abstract: Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15–17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype–phenotype map than previously anticipated.

DOI: 10.1038/s41588-021-00923-x

Source: https://www.nature.com/articles/s41588-021-00923-x

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex