Department of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Pediatrics, University of California, San Francisco, Oakland, CA, USA.
Nat Genet. 2021 Jul;53(7):972-981. doi: 10.1038/s41588-021-00879-y. Epub 2021 Jun 17.
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.
血浆脂质是已知的心血管疾病遗传风险因素，但越来越多的证据也支持其与其他器官系统疾病的遗传因素共享。我们设计了一个全面的三阶段框架，从电子病历和基因组学（347 个特征）和英国生物库（549 个特征）中识别新的与脂质相关的基因，并研究脂质、基因型、基因表达与数百种复杂人类疾病之间的关系。除了 67 个具有强复制力的新的脂质相关基因外，我们还在表型范围内发现了脂质和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 区域的不一致多效性，以及甘油三酯和痛风之间可能存在的因果关系等。我们的研究结果深入了解了血浆脂质与疾病之间关系的遗传基础，为未来的预防和治疗策略提供了依据。
