Identification of Human Brain Proteins for Bitter-Sweet Taste Perception: A Joint Proteome-Wide and Transcriptome-Wide Association Study

Abstract

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.

Differential genetic expression within reward-specific ensembles in mice

“…Contrary to the similarity in the direction of expression for Olfr1286 in both regions, Tmem245 was downregulated in male NAcore compared to the upregulation in the male PFC. Tmem245 has been linked with schizophrenic psychosis ( 51 ), which is similar to psychostimulant-induced psychosis ( 52 ). Here, we hypothesize a region-dependent role for Tmem245 in facilitating psychosis-like behavior during cocaine withdrawal linked with increasing the likelihood of seeking cocaine during periods of abstaining cocaine intake.…”

The Implications of Taste and Olfaction in Nutrition and Health

“…The authors concluded that caffeine consumption should be reduced during pregnancy and that it would be advisable to start an awareness program to avoid these negative consequences on the child's development. The association between taste sensitivity and alterations in brain structures and functions was also studied by Wei et al [34]. These authors analyzed the genetic association between the perception of sweet or bitter beverages and human brain proteins, since the perception of a bitter or sweet drink is associated with alterations in brain structure and function [35,36].…”