美国宾夕法尼亚大学Marylyn D. Ritchie研究组揭示血脂和疾病之间的新联系。2021年6月17日，国际知名学术期刊《自然—遗传学》在线发表了这一成果。

研究人员设计了一个全面的三阶段框架来鉴定新的脂质相关基因，并从电子病历和基因组学（347个特征）和英国生物银行（549个特征）中研究脂质、基因型、基因表达和数百种复杂人类疾病之间的关系。除了具有强复制的67个新的脂质相关基因外，研究人员还发现了整个表型组中脂质与疾病之间存在多效性SNP/基因的证据。其中包括脂质和多发性硬化症之间HLA区域的多效性不一致，以及甘油三酯和痛风之间的潜在因果路径等。

这些研究结果在全表型范围内深入了解了血脂与疾病之间关系的遗传基础，并可以为未来的预防和治疗策略提供背景。

据悉，血浆脂质是心血管疾病的已知遗传风险因素，但越来越多的证据也支持与其他器官系统疾病的共同遗传。

附：英文原文

Title: A unified framework identifies new links between plasma lipids and diseases from electronic medical records across large-scale cohorts

Author: Yogasudha Veturi, Anastasia Lucas, Yuki Bradford, Daniel Hui, Scott Dudek, Elizabeth Theusch, Anurag Verma, Jason E. Miller, Iftikhar Kullo, Hakon Hakonarson, Patrick Sleiman, Daniel Schaid, Charles M. Stein, Digna R. Velez Edwards, QiPing Feng, Wei-Qi Wei, Marisa W. Medina, Ronald M. Krauss, Thomas J. Hoffmann, Neil Risch, Benjamin F. Voight, Daniel J. Rader, Marylyn D. Ritchie

Issue&Volume: 2021-06-17

Abstract: Plasma lipids are known heritable risk factors for cardiovascular disease, but increasing evidence also supports shared genetics with diseases of other organ systems. We devised a comprehensive three-phase framework to identify new lipid-associated genes and study the relationships among lipids, genotypes, gene expression and hundreds of complex human diseases from the Electronic Medical Records and Genomics (347 traits) and the UK Biobank (549 traits). Aside from 67 new lipid-associated genes with strong replication, we found evidence for pleiotropic SNPs/genes between lipids and diseases across the phenome. These include discordant pleiotropy in the HLA region between lipids and multiple sclerosis and putative causal paths between triglycerides and gout, among several others. Our findings give insights into the genetic basis of the relationship between plasma lipids and diseases on a phenome-wide scale and can provide context for future prevention and treatment strategies. An analytical framework based on transcriptome-wide association and electronic medical records provides insights into the relationship between plasma lipids and complex diseases on a phenome-wide scale.

DOI: 10.1038/s41588-021-00879-y

Source: https://www.nature.com/articles/s41588-021-00879-y