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对美国非洲裔患者高甘油三酯水平的基因特征进行表征。

Characterizing genetic profiles for high triglyceride levels in U.S. patients of African ancestry.

作者信息

Jiang Lan, Gangireddy Srushti, Dickson Alyson L, Xin Yi, Yan Chao, Kawai Vivian, Cox Nancy J, Linton MacRae F, Wei Wei-Qi, Stein C Michael, Feng QiPing

出版信息

medRxiv. 2024 May 13:2024.03.11.24304107. doi: 10.1101/2024.03.11.24304107.

Abstract

Hypertriglyceridemia (HTG) is a common cardiovascular risk factor characterized by elevated circulating triglyceride (TG) levels. Researchers have assessed the genetic factors that influence HTG in studies focused predominantly on individuals of European ancestry (EA). However, relatively little is known about the contribution of genetic variation to HTG in people of AA, potentially constraining research and treatment opportunities; the lipid profile for African ancestry (AA) populations differs from that of EA populations-which may be partially attributable to genetics. Our objective was to characterize genetic profiles among individuals of AA with mild-to-moderate HTG and severe HTG versus those with normal TGs by leveraging whole genome sequencing (WGS) data and longitudinal electronic health records (EHRs) available in the All of Us (AoU) program. We compared the enrichment of functional variants within five canonical TG metabolism genes, an AA-specific polygenic risk score for TGs, and frequencies of 145 known potentially causal TG variants between patients with HTG and normal TG among a cohort of AA patients (N=15,373). Those with mild-to-moderate HTG (N=342) and severe HTG (N≤20) were more likely to carry p.S19W (OR=1.94, 95% CI [1.48-2.54], p=1.63×10 and OR=3.65, 95% CI [1.22-10.93], p=0.02, respectively) than those with normal TG. They were also more likely to have an elevated (top 10%) PRS, elevated carriage of potentially causal variant alleles, and carry any genetic risk factor. Alternative definitions of HTG yielded comparable results. In conclusion, individuals of AA with HTG were enriched for genetic risk factors compared to individuals with normal TGs.

摘要

高甘油三酯血症(HTG)是一种常见的心血管危险因素,其特征是循环甘油三酯(TG)水平升高。研究人员在主要针对欧洲血统(EA)个体的研究中评估了影响HTG的遗传因素。然而,关于遗传变异对非裔美国人(AA)HTG的贡献知之甚少,这可能会限制研究和治疗机会;非洲血统(AA)人群的血脂谱与EA人群不同,这可能部分归因于遗传学。我们的目标是通过利用“我们所有人(AoU)”项目中可用的全基因组测序(WGS)数据和纵向电子健康记录(EHR),来描述轻度至中度HTG和重度HTG的AA个体与TG正常个体的遗传特征。我们比较了15373名AA患者队列中HTG患者和TG正常患者之间五个经典TG代谢基因内功能变异的富集情况、一个AA特异性的TG多基因风险评分以及145个已知潜在因果TG变异的频率。轻度至中度HTG患者(n = 342)和重度HTG患者(n≤20)比TG正常的患者更有可能携带p.S19W(OR = 1.94,95% CI [1.48 - 2.54],p = 1.63×10 ;OR = 3.65,95% CI [1.22 - 10.93],p = 0.02)。他们也更有可能具有升高的(前10%)PRS、潜在因果变异等位基因的携带率升高以及携带任何遗传风险因素。HTG的替代定义产生了类似的结果。总之,与TG正常的个体相比,患有HTG的AA个体遗传风险因素更为富集。

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