小柯机器人

近日，荷兰格罗宁根大学Lude Franke等研究人员合作通过大规模的顺式和反式eQTL分析确定了数千个调节血液基因表达的遗传位点和多基因分值。这一研究成果于2021年9月2日在线发表在国际学术期刊《自然—遗传学》上。

为了研究基因表达的遗传学，研究人员通过eQTLGen联盟利用31,684人的血源表达进行了顺式和反式定量性状基因座（eQTL）分析。研究人员检测到了88%基因的顺式量子基因，这些基因在许多组织中都是可以重复的。远端反式QTL（在测试的10,317个性状相关变体中检测到37%）显示出较低的复制率，部分原因是复制能力低和受细胞类型组成的干扰。然而，单细胞RNA-seq数据的复制分析优先考虑了细胞内反式eQTL。

反式QTL通过几种机制发挥其作用，主要是通过转录因子的调节。13%的基因的表达与1263种表型的多基因评分相关，并准确地指出了这些性状的潜在驱动因素。总之，这项工作代表了一个大型的eQTL资源，其结果可作为深入解释复杂表型的一个起点。

据介绍，与性状相关的遗传变异主要通过转录组的调节机制影响复杂的表型。

附：英文原文

Title: Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression

Author: Vsa, Urmo, Claringbould, Annique, Westra, Harm-Jan, Bonder, Marc Jan, Deelen, Patrick, Zeng, Biao, Kirsten, Holger, Saha, Ashis, Kreuzhuber, Roman, Yazar, Seyhan, Brugge, Harm, Oelen, Roy, de Vries, Dylan H., van der Wijst, Monique G. P., Kasela, Silva, Pervjakova, Natalia, Alves, Isabel, Fav, Marie-Julie, Agbessi, Mawuss, Christiansen, Mark W., Jansen, Rick, Seppl, Ilkka, Tong, Lin, Teumer, Alexander, Schramm, Katharina, Hemani, Gibran, Verlouw, Joost, Yaghootkar, Hanieh, Snmez Flitman, Reyhan, Brown, Andrew, Kukushkina, Viktorija, Kalnapenkis, Anette, Reger, Sina, Porcu, Eleonora, Kronberg, Jaanika, Kettunen, Johannes, Lee, Bernett, Zhang, Futao, Qi, Ting, Hernandez, Jose Alquicira, Arindrarto, Wibowo, Beutner, Frank, Dmitrieva, Julia, Elansary, Mahmoud, Fairfax, Benjamin P., Georges, Michel, Heijmans, Bastiaan T., Hewitt, Alex W., Khnen, Mika, Kim, Yungil, Knight, Julian C., Kovacs, Peter, Krohn, Knut, Li, Shuang, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Momozawa, Yukihide, Mller-Nurasyid, Martina

Issue&Volume: 2021-09-02

Abstract: Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues. Distal trans-eQTL (detected for 37% of 10,317 trait-associated variants tested) showed lower replication rates, partially due to low replication power and confounding by cell type composition. However, replication analyses in single-cell RNA-seq data prioritized intracellular trans-eQTL. Trans-eQTL exerted their effects via several mechanisms, primarily through regulation by transcription factors. Expression of 13% of the genes correlated with polygenic scores for 1,263 phenotypes, pinpointing potential drivers for those traits. In summary, this work represents a large eQTL resource, and its results serve as a starting point for in-depth interpretation of complex phenotypes. Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.

DOI: 10.1038/s41588-021-00913-z

Source: https://www.nature.com/articles/s41588-021-00913-z

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