Luo Zining, Xiong Lijun, Xu Xinyu, Sun Meng, Mu Yingfei, Chen Hongjie, Liu Zhenglong, Luo Zhiyong, Wang Jianli, Liu Ying
Department of Preclinical Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, China.
Department of Stomatology, North Sichuan Medical College, Nanchong, China.
Front Nutr. 2024 May 21;11:1351067. doi: 10.3389/fnut.2024.1351067. eCollection 2024.
Existing studies have reported sustained changes in the cortical structure of rats due to coffee-related factors, which are speculated to occur in the human body. However, there is a lack of research on this topic. Additionally, previous observational studies have found the impact of diseases on cortical structure and the potential therapeutic effects of coffee on these diseases. Our aim was to study the causal effects of coffee-related factors on the human brain using SNPs (single nucleotide polymorphisms). We will connect these discovered causal effects to the impact of diseases on the brain. Through triangulating evidence, we will reveal the potential active areas of coffee in preventing diseases.
We utilized GWAS data from multiple cohorts and their databases, selecting instrumental variables for genetic prediction of coffee intake and plasma levels of caffeine and its direct metabolites. We applied these instrumental variables to individual data on cortical thickness and surface area, as well as hippocampal volume, from the ENIGMA and CHARGE consortium for Mendelian randomization analysis (MR). Triangular evidence was obtained by integrating existing evidence through a specified retrieval strategy, calculating the overlap between coffee's effects on brain regions and disease-related brain regions to identify potential regions of action.
The MR analysis yielded 93 positive results for 9 exposures, among which theobromine, a metabolite in the caffeine pathway, was found to be associated with increased hippocampal volume. For cortical structure, theobromine in the caffeine pathway was associated with a decrease in total surface area, while theobromine and caffeine in the pathway were associated with an increase in total thickness. The overlap rate of triangular evidence showed no difference in both overall and subgroup analyses, indicating a high overlap between the effects of coffee on brain regions and disease.
From predicted outcomes from causal effects, coffee intake-related factors may have lasting effects on cortical structure. Additionally, theobromine and theophylline have the greatest impact on certain brain gyri, rather than caffeine. Triangulation evidence indicates that disease and coffee intake-related factors act on the same cortical regions, suggesting the presence of potential shared or antagonistic pathways.
现有研究报道了咖啡相关因素导致大鼠皮质结构发生持续性变化，推测这种变化也会在人体中出现。然而，关于这一主题的研究尚少。此外，以往的观察性研究发现了疾病对皮质结构的影响以及咖啡对这些疾病的潜在治疗作用。我们的目的是利用单核苷酸多态性（SNP）研究咖啡相关因素对人脑的因果效应。我们将把这些发现的因果效应与疾病对大脑的影响联系起来。通过三角验证证据，我们将揭示咖啡在预防疾病方面的潜在作用区域。
我们利用了来自多个队列及其数据库的全基因组关联研究（GWAS）数据，选择用于遗传预测咖啡摄入量、血浆咖啡因及其直接代谢物水平的工具变量。我们将这些工具变量应用于来自ENIGMA和CHARGE联盟的关于皮质厚度、表面积以及海马体积的个体数据，进行孟德尔随机化分析（MR）。通过特定的检索策略整合现有证据，计算咖啡对脑区的影响与疾病相关脑区之间的重叠，以确定潜在的作用区域，从而获得三角验证证据。
MR分析对9种暴露因素产生了93个阳性结果，其中咖啡因途径中的代谢物可可碱被发现与海马体积增加有关。对于皮质结构，咖啡因途径中的可可碱与总表面积减小有关，而该途径中的可可碱和咖啡因与总厚度增加有关。三角验证证据的重叠率在总体分析和亚组分析中均无差异，表明咖啡对脑区的影响与疾病之间存在高度重叠。
从因果效应的预测结果来看，与咖啡摄入相关的因素可能对皮质结构产生持久影响。此外，可可碱和茶碱对某些脑回的影响最大，而非咖啡因。三角验证证据表明，疾病和与咖啡摄入相关的因素作用于相同的皮质区域，提示存在潜在的共同或拮抗途径。
