小柯机器人

美国布罗德研究所Patrick T. Ellinor研究组实现心脏代谢疾病和特征的罕见遗传变异分析。这一研究成果于2022年2月17日在线发表在国际学术期刊《自然—遗传学》上。

研究人员利用200337名英国生物库参与者的全外显子组测序数据，分析了罕见变异对57种疾病和26种心脏代谢特征的贡献。研究人员确定了57个基于基因的关联，并在Geisinger MyCode中广泛复制了新信号。与已知孟德尔疾病基因的突变相关风险非常突出，包括MYBPC3、LDLR、GCK、PKD1和TTN。许多基因显示出罕见和常见变异证据的独立融合，包括GIGYF1和2型糖尿病之间的关联。研究人员发现身高和18个与血脂或葡萄糖水平相关的独特基因有几个大的效应关联。

最后，研究人员发现有1.0%至2.4%的参与者携带有心脏代谢疾病的罕见潜在致病变体。这些发现可能有助于旨在治疗和筛查这些常见疾病的研究。

据了解，心脏代谢性疾病是全世界死亡的主要原因。尽管有已知的遗传因素，但人们对这些疾病的了解仍然不完整。

附：英文原文

Title: Analysis of rare genetic variation underlying cardiometabolic diseases and traits among 200,000 individuals in the UK Biobank

Author: Jurgens, Sean J., Choi, Seung Hoan, Morrill, Valerie N., Chaffin, Mark, Pirruccello, James P., Halford, Jennifer L., Weng, Lu-Chen, Nauffal, Victor, Roselli, Carolina, Hall, Amelia W., Oetjens, Matthew T., Lagerman, Braxton, vanMaanen, David P., Aragam, Krishna G., Lunetta, Kathryn L., Haggerty, Christopher M., Lubitz, Steven A., Ellinor, Patrick T.

Issue&Volume: 2022-02-17

Abstract: Cardiometabolic diseases are the leading cause of death worldwide. Despite a known genetic component, our understanding of these diseases remains incomplete. Here, we analyzed the contribution of rare variants to 57 diseases and 26 cardiometabolic traits, using data from 200,337 UK Biobank participants with whole-exome sequencing. We identified 57 gene-based associations, with broad replication of novel signals in Geisinger MyCode. There was a striking risk associated with mutations in known Mendelian disease genes, including MYBPC3, LDLR, GCK, PKD1 and TTN. Many genes showed independent convergence of rare and common variant evidence, including an association between GIGYF1 and type 2 diabetes. We identified several large effect associations for height and 18 unique genes associated with blood lipid or glucose levels. Finally, we found that between 1.0% and 2.4% of participants carried rare potentially pathogenic variants for cardiometabolic disorders. These findings may facilitate studies aimed at therapeutics and screening of these common disorders. Analysis of whole-exome sequencing data from over 200,000 individuals in the UK Biobank provides new insights into the contribution of rare variants to cardiometabolic diseases and traits.

DOI: 10.1038/s41588-021-01011-w

Source: https://www.nature.com/articles/s41588-021-01011-w

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