期刊
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
卷 29, 期 18, 页码 2374-2385出版社
OXFORD UNIV PRESS
DOI: 10.1093/eurjpc/zwac219
关键词
Apolipoprotein B; Non-HDL cholesterol; Coronary artery disease; Mendelian randomization
资金
- NordForsk [90580]
- Innovation Fund Denmark (IFD) [8114-00033B]
The study showed that many sequence variants have discordant effects on non-HDL-C and apoB, demonstrating that the causal mechanism underlying the relationship between apolipoprotein B particles and CAD is more associated with non-HDL-C.
Background and aims The causal contribution of apolipoprotein B (apoB) particles to coronary artery disease (CAD) is established. We examined whether this atherogenic contribution is better reflected by non-high-density lipoprotein cholesterol (non-HDL-C) or apoB particle concentration. Method and results We performed Mendelian randomization (MR) analysis using 235 variants as genetic instruments; testing the relationship between their effects on the exposures, non-HDL-C and apoB, and on the outcome CAD using weighted regression. Variant effect estimates on the exposures came from the UK Biobank (N = 376 336) and on the outcome from a meta-analysis of five CAD datasets (187 451 cases and 793 315 controls). Subsequently, we carried out sensitivity and replication analyses. In univariate MR analysis, both exposures associated with CAD (beta(non-HDL-C) = 0.40, P = 2.8 x 10(-48) and beta(apoB) = 0.38, P = 1.3 x 10(-44)). Adding effects on non-HDL-C into a model that already included those on apoB significantly improved the genetically predicted CAD effects (P = 3.9 x 10(-5)), while adding apoB into the model including non-HDL-C did not (P = 0.69). Thirty-five per cent (82/235) of the variants used as genetic instruments had discordant effects on the exposures, associating with non-HDL-C/apoB ratio at P < 2.1 x 10(-4) (0.05/235). Fifty-one variants associated at genome-wide significance. Conclusion Many sequence variants have discordant effects on non-HDL-C and apoB. These variants allowed us to show that the causal mechanism underlying the relationship between apolipoprotein B particles and CAD is more associated with non-HDL-C than apoB particle concentration.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据