Exploring the causal pathway from omega-6 levels to coronary heart disease: A network Mendelian randomization study
Exploring the causal pathway from omega-6 levels to coronary heart disease: A network Mendelian randomization study
复制标题
探索 omega-6 水平与冠心病的因果关系：网络孟德尔随机化研究
DOI：
10.1016/j.numecd.2019.09.013
复制
发表时间：
2020-02-10
影响因子：
3.9
通讯作者：
Liao, Xin-xue
中科院分区：
文献类型：
--
作者：
Liao, Li-zhen;Li, Wei-dong;Liao, Xin-xue
背景和目的：关于omega-6脂肪对冠心病(CHD)风险的影响的证据仍然没有定论。我们应用网络MR框架来确定omega-6水平与CHD之间的因果关系，以及潜在的胆固醇代谢风险因素(总胆固醇，TC；低密度脂蛋白胆固醇，LDL-C；高密度脂蛋白胆固醇，HDLC；甘油三酯，TG)，这些因素可能在omega-6水平与CHD之间的联系中起中介作用，通过整合汇总水平的全基因组关联研究(GWAS)数据。方法和结果：网络MR分析-一种使用遗传变量作为暴露和中介变量来推断因果关系的方法，以检验omega-6水平与CHD和胆固醇代谢风险因素之间的因果关系。来自Kettunen等人的汇总统计数据。对于omega-6(n=13506)，使用CARDIoGRAMplusC4D联合体数据(n=184305)，使用GLGC联合体数据(n=108363)，用于TC、LDLC、HDLc和TG。IVW方法的估计表明，在omega-6中，每增加一个标准差，冠心病的优势比(OR)(95%可信区间[CI])为1.210(1.118-1.310)。MR Egger法(OR，1.418；95%CI，1.087~1.851；P=0.050)和加权中位法(OR，1.239；95%CI，1.125~1.364；P=0.000)结果一致。Omega-6与TC、LDL-C、TG呈正相关，与高密度脂蛋白无相关性。此外，TC、LDL-C和TG与CHD呈正相关。结论：利用网络MR框架，我们提供了支持omega-6与CHD之间正向因果关系的证据，这种关系可能部分由TC、LDL-C和TG介导。(C)2019年意大利糖尿病学会、意大利动脉粥样硬化研究学会、意大利人类营养学会和费德里科二世大学临床内外科。爱思唯尔出版公司(Elsevier B.V.)
Background and aims: Evidence on the effect of omega-6 fats on coronary heart disease (CHD) risk remains inconclusive. We applied a network MR framework to determine the causal effects between omega-6 levels and CHD and the potential cholesterol metabolic risk factors (Total cholesterol, TC; Low-density lipoprotein cholesterol, LDL-C; High-density lipoprotein cholesterol, HDL-C; Triglycerides, TG) which might act as mediators in the link between omega-6 levels and CHD by integrating summary-level genome wide association study (GWAS) data.Methods and results: Network MR analysis-an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality was performed to examine the causal effects between omega-6 levels and CHD and cholesterol metabolic risk factors. Summary statistics from the Kettunen et al. 's consortium were used (n = 13506) for omega-6, CARDIoGRAMplusC4D consortium data were used (n = 184305) for CHD, and GLGC consortia data were used (n = 108363) for TC, LDL-C, HDL-C, and TG. The IVW method estimate indicated that the odds ratio (OR) (95% confidence interval [CI]) for CHD was 1.210 (1.118-1.310) per standard deviation increase in omega-6. Results were consistent in MR Egger method (OR, 1.418; 95% CI, 1.087-1.851; P = 0.050) and weighted median methods (OR, 1.239; 95% CI, 1.125-1.364; P = 0.000). Omega-6 was positively causal associated with TC, LDL-C, and TG but was not associated with HDL-C. Moreover, TC, LDL-C, and TG were positively associated with CHD.Conclusions: Using a network MR framework, we provided evidence supporting a positive causal relationship between omega-6 and CHD, which might be partially mediated by TC, LDL-C, and TG. (C) 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V.