血清脂质体特征与颅内动脉瘤风险的关系：孟德尔随机研究

IF 4.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Neurochemistry Pub Date : 2024-10-25 DOI:10.1111/jnc.16247

Mingqin Zhang, Dongyi Yang, Jiabin Wang, Dan Wang, Jin Xu, Yibo Wang

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引用次数: 0

摘要

采用双样本孟德尔随机化（MR）分析法评估脂质体特征与颅内动脉瘤（IAs）风险之间的因果关系。从已发表的全基因组关联研究（GWAS）或IEU开放式GWAS项目中获得了与脂质组特征（227个成分）和IA[仅动脉瘤性蛛网膜下腔出血（aSAH），仅未破裂的IA（uIA）]相关的遗传变异，并将其作为MR分析的工具变量。主要分析采用逆方差加权法得出因果关系估计值，并以带 95% 置信区间 (CI) 的比值比 (OR) 表示。在这 227 项脂质组学特征中，只有基因预测的高水平胆固醇与极小极低密度脂蛋白（VLDL）中总脂质的比率[OR = 0.629 (95% CI, 0.504-0.786)], 胆固醇酯与极小极低密度脂蛋白中总脂质的比率[OR = 0.637 (95% CI, 0.509-0.797)], 二十二碳六烯酸与总脂肪酸的比率[OR = 0.691（95% CI，0.582-0.820）]和多不饱和脂肪酸与单不饱和脂肪酸之比[OR = 0.630（95% CI，0.522-0.760）]可降低罹患 aSAH 的风险，而基因预测的单不饱和脂肪酸与总脂肪酸之比偏高[OR = 1.471（95% CI，1.215-1.781）]则会增加罹患 aSAH 的风险。此外，遗传预测的高水平胆固醇与极小 VLDL 中总脂类的比率[OR = 0.657 (95% CI, 0.542-0.798)], 胆固醇酯与极小 VLDL 中总脂类的比率[OR = 0.663 (95% CI, 0.548-0.803)], 游离胆固醇与极小 VLDL 中总脂类的比率[OR = 0.682（95% CI，0.560-0.832）]、小 VLDL 中磷脂与总脂的比率[OR = 0.674（95% CI，0.548-0.830）]和多不饱和脂肪酸与单不饱和脂肪酸的比率[OR = 0.678（95% CI，0.569-0.808）]降低了 IA 的风险。多变量磁共振结果表明，在调整收缩压和每日吸烟量后，这些因果关系依然存在。血清脂质对IA和aSAH的影响可能主要是由VLDL等亚类脂质引起的。

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Association of serum lipidomic profiles with risk of intracranial aneurysm: A Mendelian randomization study.

A two-sample Mendelian randomization (MR) analysis was utilized to assess the causal relationship between lipidomic profiles and the risk of intracranial aneurysms (IAs). Genetic variants related to lipidomic profiles (227 components) and IA [IA, aneurysmal subarachnoid hemorrhage (aSAH) only, unruptured IA (uIA) only] were obtained from published genome-wide association studies (GWASs) or the IEU Open GWAS project and used as instrumental variables for MR analysis. The inverse-variance weighted method was used in the primary analyses to derive causality estimates and was expressed as odds ratio (OR) with 95% confidence interval (CI). Of these 227 lipidomic profiles, only genetically predicted high levels of cholesterol to total lipids ratio in very small very-low-density lipoproteins (VLDL) [OR = 0.629 (95% CI, 0.504-0.786)], cholesteryl esters to total lipids ratio in very small VLDL [OR = 0.637 (95% CI, 0.509-0.797)], ratio of docosahexaenoic acid to total fatty acids [OR = 0.691 (95% CI, 0.582-0.820)], and ratio of polyunsaturated fatty acids to monounsaturated fatty acids [OR = 0.630 (95% CI, 0.522-0.760)] reduced the risk of aSAH, whereas genetically predicted high ratio of monounsaturated fatty acids to total fatty acids [OR = 1.471 (95% CI, 1.215-1.781)] increased the risk of aSAH. Moreover, genetically predicted high levels of cholesterol to total lipids ratio in very small VLDL [OR = 0.657 (95% CI, 0.542-0.798)], cholesteryl esters to total lipids ratio in very small VLDL [OR = 0.663 (95% CI, 0.548-0.803)], free cholesterol to total lipids ratio in small VLDL [OR = 0.682 (95% CI, 0.560-0.832)], phospholipids to total lipids ratio in small VLDL [OR = 0.674 (95% CI, 0.548-0.830)], and ratio of polyunsaturated fatty acids to monounsaturated fatty acids [OR = 0.678 (95% CI, 0.569-0.808)] reduced the risk of IA. The results of multivariable MR demonstrated that these causal associations persisted after adjusting for systolic blood pressure and cigarettes smoked per day. The effect of serum lipids on IA and aSAH may be mainly caused by subclasses of lipids such as VLDL.

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来源期刊

Journal of Neurochemistry 医学-神经科学

CiteScore

9.30

自引率

2.10%

发文量

181

审稿时长

2.2 months

期刊介绍： Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.