普通人群高低密度脂蛋白胆固醇和缺血性心脏病的多基因风险

IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Atherosclerosis Pub Date : 2024-08-28 DOI:10.1016/j.atherosclerosis.2024.118574
Tim Møller Eyrich , Nawar Dalila , Mette Christoffersen , Anne Tybjærg-Hansen , Stefan Stender
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引用次数: 0

摘要

背景和目的我们测试了丹麦普通人群中低密度脂蛋白胆固醇(LDL-C)和冠状动脉疾病(CAD)的多基因风险评分(PRS)与 LDL-C 和缺血性心脏病(IHD)风险的关联。每个人的低密度脂蛋白-PRS和中密度脂蛋白-CAD-PRS都是基于400,000个变体计算得出的。我们还对已知会导致家族性高胆固醇血症(FH)的 LDLR 或 APOB 中的四个罕见变体进行了基因分型。结果 APOB 或 LDLR 中导致 FH 的变体的杂合子携带者的平均 LDL-C 分别为 5.40 和 6.09 mmol/L,与非携带者相比,IHD 的几率比为 2.27(95 % CI 1.43-3.51)。LDL-PRS 解释了队列中 LDL-C 总变化的 13.8%。LDL-PRS 最低和最高 1% 的个体的平均 LDL-C 分别为 2.49 和 4.75 mmol/L。与中间 20-80% 的人群相比,LDL-PRS 最低和最高 1% 的人群患 IHD 的几率比分别为 0.58(95% CI,0.38-0.88)和 1.83(95% CI,1.33-2.53)。结论 LDL-PRS 和 CAD-PRS 的前 1% 对 LDL-C 和 IHD 风险的影响与 APOB 或 LDLR 中罕见的 FH 致病变异携带者的影响相当。这些结果凸显了在临床上实施此类PRS的潜在价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Polygenic risk of high LDL cholesterol and ischemic heart disease in the general population

Background and aims

We tested the association of polygenic risk scores (PRS) for low-density lipoprotein cholesterol (LDL-C) and coronary artery disease (CAD) with LDL-C and risk of ischemic heart disease (IHD) in the Danish general population.

Methods

We included a total of 21,485 individuals from the Copenhagen General Population Study and Copenhagen City Heart Study. For everyone, LDL-PRS and CAD-PRS were calculated, each based on >400,000 variants. We also genotyped four rare variants in LDLR or APOB known to cause familial hypercholesterolemia (FH).

Results

Heterozygous carriers of FH-causing variants in APOB or LDLR had a mean LDL-C of 5.40 and 6.09 mmol/L, respectively, and an odds ratio for IHD of 2.27 (95 % CI 1.43–3.51) when compared to non-carriers. The LDL-PRS explained 13.8 % of the total variation in LDL-C in the cohort. Individuals in the lowest and highest 1 % of LDL-PRS had a mean LDL-C of 2.49 and 4.75 mmol/L, respectively. Compared to those in the middle 20–80 %, those in the lowest and highest 1 % of LDL-PRS had odds ratios for IHD of 0.58 (95 % CI, 0.38–0.88) and 1.83 (95 % CI, 1.33–2.53). The corresponding odds ratios for CAD-PRS were 0.61 (95 % CI, 0.41–0.92) and 2.06 (95 % CI, 1.49–2.85).

Conclusions

The top 1 % of LDL-PRS and CAD-PRS conferred effects on LDL-C and risk of IHD comparable to those seen for carriers of rare FH-causing variants in APOB or LDLR. These results highlight the potential value of implementing such PRS clinically.

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来源期刊
Atherosclerosis
Atherosclerosis 医学-外周血管病
CiteScore
9.80
自引率
3.80%
发文量
1269
审稿时长
36 days
期刊介绍: Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.
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