PDF(Pubmed)
Abstract：
Hypertriglyceridemia (HTG) is a common cardiovascular risk factor characterized by elevated triglyceride (TG) levels. Researchers have assessed the genetic factors that influence HTG in studies focused predominantly on individuals of European ancestry. However, relatively little is known about the contribution of genetic variation of HTG in people of African ancestry (AA), potentially constraining research and treatment opportunities. 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 data and longitudinal electronic health records available in the All of Us 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 HTG patients 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 APOA5 p.S19W (odds ratio = 1.94, 95% confidence interval = [1.48-2.54], P = 1.63 × 10-6 and OR = 3.65, 95% confidence interval: [1.22-10.93], P = 0.02, respectively) than those with normal TG. They were also more likely to have an elevated (top 10%) polygenic risk score, 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,对AA人群中遗传变异对HTG的贡献知之甚少，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人群的血脂谱不同，这可能部分归因于遗传学。我们的目标是通过利用全基因组测序（WGS）数据和“所有人”中提供的纵向电子健康记录（EHR）来表征具有轻度至中度HTG和重度HTG的AA个体与具有正常TG的个体之间的遗传特征（AoU）计划。我们比较了五个典型TG代谢基因中功能变体的富集，TG的AA特异性多基因风险评分，以及一组AA患者中HTG患者和正常TG患者之间145种已知潜在因果TG变异的频率（N=15,373）。轻度至中度HTG（N=342）和重度HTG（N≤20）的患者更可能携带APOA5p.S19W（OR=1.94，95％CI[1.48-2.54]，p=1.63×10-6，OR=3.65，95%CI[1.22-10.93]，分别为p=0.02）比TG正常的那些。他们的PRS也更有可能升高(前10%)，潜在因果变异等位基因的携带升高，并携带任何遗传风险因素。HTG的替代定义产生了可比的结果。总之,与具有正常TG的个体相比，具有HTG的AA个体的遗传危险因素得到了富集。
