小柯机器人

西湖大学生命科学学院杨剑团队报道了RNA剪接的遗传控制及其在复杂性状变异中的独特作用。相关论文于2022年8月18日发表在《自然—遗传学》杂志上。

他们介绍了一种 sQTL 映射方法，测试异构体-表达数量性状基因座 (eQTL) 效应 (THISTLE) 之间的异质性，与竞争方法相比具有更高的能力。将 THISTLE 与互补 剪接QTL (sQTL)作图策略一起应用于脑转录组 (n = 2,865) 和基因型数据，他们在 P < 5 × 10⁻⁸ 处鉴定了 12,794 个具有 cis-sQTL 的基因，其中约 61% 与 eQTL 不同。将 sQTL 数据整合到 GWAS 中的 12 个与大脑相关的复杂性状（包括疾病），他们通过 cis-sQTLs 确定了与这些性状相关的 244 个基因，其中大约 61% 无法使用相应的 eQTL 数据发现。他们的研究证明了大多数 sQTL 在转录和复杂性状变异的遗传调控中的独特作用。

据了解，从人类全基因组关联研究 (GWAS) 中发现的大多数遗传变异都是非编码的，表明它们在基因调控中的作用。先前的研究表明 GWAS 信号与eQTL存在相当大的联系，但与其他遗传调控机制的联系，例如sQTL，尚未得到充分探索。

附：英文原文

Title: Genetic control of RNA splicing and its distinct role in complex trait variation

Author: Qi, Ting, Wu, Yang, Fang, Hailing, Zhang, Futao, Liu, Shouye, Zeng, Jian, Yang, Jian

Issue&Volume: 2022-08-18

Abstract: Most genetic variants identified from genome-wide association studies (GWAS) in humans are noncoding, indicating their role in gene regulation. Previous studies have shown considerable links of GWAS signals to expression quantitative trait loci (eQTLs) but the links to other genetic regulatory mechanisms, such as splicing QTLs (sQTLs), are underexplored. Here, we introduce an sQTL mapping method, testing for heterogeneity between isoform-eQTL effects (THISTLE), with improved power over competing methods. Applying THISTLE together with a complementary sQTL mapping strategy to brain transcriptomic (n=2,865) and genotype data, we identified 12,794 genes with cis-sQTLs at P<5×108, approximately 61% of which were distinct from eQTLs. Integrating the sQTL data into GWAS for 12 brain-related complex traits (including diseases), we identified 244 genes associated with the traits through cis-sQTLs, approximately 61% of which could not be discovered using the corresponding eQTL data. Our study demonstrates the distinct role of most sQTLs in the genetic regulation of transcription and complex trait variation.

DOI: 10.1038/s41588-022-01154-4

Source: https://www.nature.com/articles/s41588-022-01154-4

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
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