Li Jiayi, Xia Kailin, Wang Zhengrui, Liu Yanru, Tong Yicheng, Wang Yuwei, Zhou Yumou, Zhang Linjing, Tang Lu, Fan Dongsheng, Yang Qiong
Department of Neurology, Peking University Third Hospital, Beijing, China.
Peking University Health Science Center, Beijing, China.
Front Nutr. 2023 Jun 22;10:1172587. doi: 10.3389/fnut.2023.1172587. eCollection 2023.
Previous studies have suggested a potential association between nutrients and cerebral small vessel disease (CSVD), but this association has not been fully addressed.
We intended to clarify the causal associations between four categories of essential nutrients (amino acids, polyunsaturated fatty acids, minerals and vitamins) and two acute manifestations of CSVD (intracerebral hemorrhage and small vessel stroke) using two-sample Mendelian randomization (MR) analysis.
We obtained European-based large-scale genome-wide association studies (GWASs) related to CSVD (6,255 cases and 233,058 controls) and nutrient concentrations. Causality evaluation mainly included the results of the inverse variance-weighted (IVW) method. The simple median method, the weighted median method and the MR-Egger method were adopted for sensitivity analyses.
For ICH or SVS, increased levels of phenylalanine (OR = 1.188, < 0.001) and dihomo-gamma-linolenic acid (DGLA) (OR = 1.153, = 0.001) showed risk effects, while docosapentaenoic acid (DPA) (OR = 0.501, < 0.001), zinc (OR = 0.919, < 0.001), and arachidonic acid (OR = 0.966, = 0.007) showed protective effects. For lobar hemorrhage or SVS, AA (OR = 0.978, < 0.001), zinc (OR = 0.918, < 0.001), and retinol (OR = 0.753, < 0.001) showed risk effects; DPA (OR = 0.682, = 0.022), gamma-linolenic acid (OR = 0.120, = 0.033) and 25(OH)D (OR = 0.874, = 0.040) showed protective effects. For nonlobar hemorrhage or SVS, DGLA (OR = 1.088, < 0.001) and phenylalanine (OR = 1.175, = 0.001) showed risk effects.
Our study analyzed the effect of nutrients on CSVD risk from a genetic perspective, with implications for CSVD prevention through nutrient supplementation.
先前的研究表明营养素与脑小血管疾病（CSVD）之间可能存在关联，但这种关联尚未得到充分探讨。
我们旨在通过两样本孟德尔随机化（MR）分析阐明四类必需营养素（氨基酸、多不饱和脂肪酸、矿物质和维生素）与CSVD的两种急性表现（脑出血和小血管卒中）之间的因果关系。
我们获取了基于欧洲的与CSVD相关的大规模全基因组关联研究（GWASs）（6255例病例和233058例对照）以及营养素浓度数据。因果关系评估主要包括逆方差加权（IVW）方法的结果。敏感性分析采用简单中位数法、加权中位数法和MR-Egger法。
对于脑出血或小血管卒中，苯丙氨酸水平升高（OR = 1.188，<0.001）和二高-γ-亚麻酸（DGLA）（OR = 1.153，= 0.001）显示出风险效应，而二十二碳五烯酸（DPA）（OR = 0.501，<0.001）、锌（OR = 0.919，<0.001）和花生四烯酸（OR = 0.966，= 0.007）显示出保护作用。对于脑叶出血或小血管卒中，花生四烯酸（AA）（OR = 0.978，<0.001）、锌（OR = 0.918，<0.001）和视黄醇（OR = 0.753，<0.001）显示出风险效应；DPA（OR = 0.682，= 0.022）、γ-亚麻酸（OR = 0.120，= 0.033）和25(OH)D（OR = 0.874，= 0.040）显示出保护作用。对于非脑叶出血或小血管卒中，DGLA（OR = 1.088，<0.001）和苯丙氨酸（OR = 1.175，= 0.001）显示出风险效应。
我们的研究从遗传学角度分析了营养素对CSVD风险的影响，对通过补充营养素预防CSVD具有启示意义。
