小柯机器人

日本东京大学Issei Komuro等研究人员合作发现，房颤的跨祖先全基因组分析揭示疾病生物学并实现心脏病风险预测。相关论文于2023年1月19日在线发表在《自然—遗传学》杂志上。

研究人员在日本人口中进行了全基因组关联研究，包括150272人中的9826个病例，并确定了与房颤有关的东亚特有的罕见变异。对包括77690个病例在内的100多万人进行了跨血统元分析，发现了35个新的易感基因座。全转录组关联分析确定IL6R是一个假定的致病基因，表明免疫反应的参与。与ChIP-seq数据的整合分析和使用人类诱导多能干细胞衍生的心肌细胞功能评估表明ERRg在房颤相关基因的转录调控中具有关键作用。从跨家系荟萃分析中得出的多基因风险评分预测了心血管和中风死亡风险的增加，并在未诊断的房颤患者中分离出患有心肌栓塞性中风的个体。这些结果为房颤遗传学提供了新的生物和临床见解，并表明其在临床应用方面的潜力。。

据介绍，房颤是一种常见的心律失常，导致中风的风险增加。尽管病因具有高度的遗传性，但人们对房颤的遗传结构的理解仍然不完整。

附：英文原文

Title: Cross-ancestry genome-wide analysis of atrial fibrillation unveils disease biology and enables cardioembolic risk prediction

Author: Miyazawa, Kazuo, Ito, Kaoru, Ito, Masamichi, Zou, Zhaonan, Kubota, Masayuki, Nomura, Seitaro, Matsunaga, Hiroshi, Koyama, Satoshi, Ieki, Hirotaka, Akiyama, Masato, Koike, Yoshinao, Kurosawa, Ryo, Yoshida, Hiroki, Ozaki, Kouichi, Onouchi, Yoshihiro, Takahashi, Atsushi, Matsuda, Koichi, Murakami, Yoshinori, Aburatani, Hiroyuki, Kubo, Michiaki, Momozawa, Yukihide, Terao, Chikashi, Oki, Shinya, Akazawa, Hiroshi, Kamatani, Yoichiro, Komuro, Issei

Issue&Volume: 2023-01-19

Abstract: Atrial fibrillation (AF) is a common cardiac arrhythmia resulting in increased risk of stroke. Despite highly heritable etiology, our understanding of the genetic architecture of AF remains incomplete. Here we performed a genome-wide association study in the Japanese population comprising 9,826 cases among 150,272 individuals and identified East Asian-specific rare variants associated with AF. A cross-ancestry meta-analysis of >1 million individuals, including 77,690 cases, identified 35 new susceptibility loci. Transcriptome-wide association analysis identified IL6R as a putative causal gene, suggesting the involvement of immune responses. Integrative analysis with ChIP-seq data and functional assessment using human induced pluripotent stem cell-derived cardiomyocytes demonstrated ERRg as having a key role in the transcriptional regulation of AF-associated genes. A polygenic risk score derived from the cross-ancestry meta-analysis predicted increased risks of cardiovascular and stroke mortalities and segregated individuals with cardioembolic stroke in undiagnosed AF patients. Our results provide new biological and clinical insights into AF genetics and suggest their potential for clinical applications.

DOI: 10.1038/s41588-022-01284-9

Source: https://www.nature.com/articles/s41588-022-01284-9

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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