Susceptibility gene identification and risk evaluation model construction by transcriptome-wide association analysis for salt sensitivity of blood pressure.

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. METHODS AND RESULTS: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets. CONCLUSIONS: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals.

Interpretation of the phenolation and structural changes of lignin in a novel ternary deep eutectic solvent.

Deep eutectic solvents (DES) are promising green solvents for depolymerization and reconstruction of lignin. Revealing the transformations of lignin during DES treatment is beneficial for high potential lignin applications. In this study, bagasse lignin was treated with a binary DES and three ternary DESs, respectively. The results showed that net hydrogen bonding acidity(α-ß) value of DES was positively correlated to the increment of phenolic hydroxyl of lignin, and the ternary DES of choline chloride-formic acid-oxalic acid (ChCl-FA-OA) exhibited the best phenolation performances. The phenolic hydroxyl content of ChCl-FA-OA treated lignin was increased by 50.4 %, reaching 2.41 mmol/g under optimum conditions (120 °C, 4 h, ChCl-FA-OA = 1:2:1). Moreover, it was found that the cleavage of ß-O-4' aryl ether bond and ester bond were dominant reactions during the treatment, accompanied by condensation reactions. Additionally, the obtained lignin oil contained various syringyl and guaiacyl derived phenolic compounds. Especially, the content of acetovanillone in lignin oil reached 29.94 %, much higher than in previous studies. Finally, the degradation mechanism of lignin in ChCl-FA-OA system was proposed. The present work provided insights into the relationship between lignin phenolation and DES properties. The novel ChCl-FA-OA system can achieve efficient lignin depolymerization, and convert lignin biomass into value-added chemical products.