■尽管观察性研究表明脂肪酸(FAs)与阿尔茨海默病和痴呆之间存在联系,关于这些关系如何延伸到路易体痴呆(DLB)的不确定性仍然存在。
■为了探索FAs与DLB发展之间的潜在因果关系,从而使用遗传工具来推断因果关系来澄清这些关联。
■我们应用了双样本孟德尔随机化(MR)和多变量孟德尔随机化(MVMR)方法。遗传数据来自DLB队列,包括2,591例和4,027个欧洲血统对照。八个FAs,包括亚油酸,二十二碳六烯酸,单不饱和脂肪酸,omega-3脂肪酸,omega-6脂肪酸,多不饱和脂肪酸,饱和脂肪酸,和总脂肪酸,是从英国生物银行的代谢生物标志物的全面GWAS中获得的,由夜莺健康于2020年(met-d)进行,涉及114,999人。我们的分析包括逆方差加权,MR-Egger,加权中位数,简单模式,和加权模式MR估计。Cochran的Q统计,MR-PRESSO,和MR-Egger截距检验用于量化工具变量的异质性和水平多效性。
■在单变量MR中,只有亚油酸与发展为DLB的风险具有显着的遗传关联。亚油酸的比值比为1.337,95%置信区间为1.019-1.756(pIVW=0.036)。MVMR的结果表明,没有FA与DLB的发生率相关。
■结果不支持FA可以降低发展DLB的风险的假设。然而,阐明FAs与DLB风险之间的关系对于告知DLB的饮食建议和治疗方法具有潜在意义。
UNASSIGNED: Although observational studies indicated connections between fatty acids (FAs) and Alzheimer\'s disease and dementia, uncertainty persists regarding how these relationships extend to dementia with Lewy bodies (DLB).
UNASSIGNED: To explore the potential causal relationships between FAs and the development of DLB, thus clarifying these associations using genetic instruments to infer causality.
UNASSIGNED: We applied a two-sample Mendelian randomization (MR) and multivariable Mendelian randomization (MVMR) approach. Genetic data were obtained from a DLB cohort, comprising 2,591 cases and 4,027 controls of European descent. Eight FAs, including linoleic acid, docosahexaenoic acid, monounsaturated fatty acid, omega-3 fatty acid, omega-6 fatty acid, polyunsaturated fatty acid, saturated fatty acid, and total fatty acid, were procured from a comprehensive GWAS of metabolic biomarkers of UK Biobank, conducted by Nightingale Health in 2020 (met-d), involving 114,999 individuals. Our analysis included inverse-variance weighted, MR-Egger, weighted-median, simple mode, and weighted-mode MR estimates. Cochran\'s Q-statistics, MR-PRESSO, and MR-Egger intercept test were used to quantify the heterogeneity and horizontal pleiotropy of instrumental variables.
UNASSIGNED: Only linoleic acid showed a significant genetic association with the risk of developing DLB in the univariate MR. The odds ratio for linoleic acid was 1.337 with a 95% confidence interval of 1.019-1.756 (pIVW = 0.036). Results from the MVMR showed that no FAs were associated with the incidence of DLB.
UNASSIGNED: The results did not support the hypothesis that FAs could reduce the risk of developing DLB. However, elucidating the relationship between FAs and DLB risk holds potential implications for informing dietary recommendations and therapeutic approaches in DLB.