Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
Nutrients. 2022 May 23;14(10):2177. doi: 10.3390/nu14102177.
Objective: Bitter or sweet beverage perception is associated with alterations in brain structure and function. Our aim is to analyze the genetic association between bitter or sweet beverage perception and human brain proteins. Materials and methods: In our study, 8356 and 11,518 proteins were first collected from two reference datasets of human brain proteomes, the ROS/MAP and Banner. The bitter or sweet beverage perception-related proteome-wide association studies (PWAS) were then conducted by integrating recent genome-wide association study (GWAS) data (n = 422,300) of taste perception with human brain proteomes. The human brain gene expression profiles were collected from two reference datasets, including the brain RNA-seq (CBR) and brain RNA-seq splicing (CBRS). The taste perception-related transcriptome-wide association studies (TWAS) were finally performed by integrating the same GWAS data with human brain gene expression profiles to validate the PWAS findings. Results: In PWAS, four statistically significant proteins were identified using the ROS/MAP and then replicated using the Banner reference dataset (all permutated p < 0.05), including ABCG2 for total bitter beverages and tea, CPNE1 for total bitter beverage, ACTR1B for artificially sweetened beverages, FLOT2 for alcoholic bitter beverages and total sweet beverages. In TWAS analysis, six statistically significant genes were detected by CBR and confirmed by the CBRS reference dataset (all permutated p < 0.05), including PIGG for total bitter beverages and non-alcoholic bitter beverages, C3orf18 for total bitter beverages, ZSWIM7 for non-alcoholic bitter beverages, PEX7 for coffee, PKP4 for tea and RPLP2 for grape juice. Further comparison of the PWAS and TWAS found three common statistically significant proteins/genes identified from the Banner and CBR reference datasets, including THBS4 for total bitter beverages, CA4 for non-alcoholic bitter beverages, LIAS for non-grape juices. Conclusions: Our results support the potential effect of bitter or sweet beverage perception on brain function and identify several candidate brain proteins for bitter or sweet beverage perception.
苦味或甜味饮料的感知与大脑结构和功能的改变有关。我们的目的是分析苦味或甜味饮料感知与人类大脑蛋白质之间的遗传关联。
在我们的研究中，首先从人类大脑蛋白质组的两个参考数据集 ROS/MAP 和 Banner 中收集了 8356 种和 11518 种蛋白质。然后，通过整合味觉感知的最近全基因组关联研究（GWAS）数据（n=422300）与人类大脑蛋白质组，进行苦味或甜味饮料感知的全蛋白质组关联研究（PWAS）。人类大脑基因表达谱从两个参考数据集收集，包括大脑 RNA-seq（CBR）和大脑 RNA-seq 剪接（CBRS）。最后，通过整合相同的 GWAS 数据与人类大脑基因表达谱进行味觉感知的转录组全关联研究（TWAS），验证 PWAS 的发现。
在 PWAS 中，使用 ROS/MAP 鉴定了 4 种具有统计学意义的蛋白质，然后使用 Banner 参考数据集进行了复制（所有置换 p<0.05），包括 ABCG2 用于总苦味饮料和茶，CPNE1 用于总苦味饮料，ACTR1B 用于人工甜味饮料，FLOT2 用于酒精苦味饮料和总甜味饮料。在 TWAS 分析中，使用 CBR 检测到 6 个具有统计学意义的基因，并通过 CBRS 参考数据集得到确认（所有置换 p<0.05），包括 PIGG 用于总苦味饮料和非酒精苦味饮料，C3orf18 用于总苦味饮料，ZSWIM7 用于非酒精苦味饮料，PEX7 用于咖啡，PKP4 用于茶和 RPLP2 用于葡萄汁。对 PWAS 和 TWAS 的进一步比较发现，从 Banner 和 CBR 参考数据集鉴定出 3 个具有统计学意义的共同蛋白质/基因，包括 THBS4 用于总苦味饮料，CA4 用于非酒精苦味饮料，LIAS 用于非葡萄汁。
我们的研究结果支持苦味或甜味饮料感知对大脑功能的潜在影响，并确定了几个苦味或甜味饮料感知的候选大脑蛋白质。
