The gut microbiome and host genetics are both associated with major depressive disorder (MDD); however, the molecular mechanisms among the associations are poorly understood, especially in the Asian, Chinese group. Our study applied linear discriminant analysis (LDA) effect size (LEfSe) and genome-wide association analysis in the cohort with both gut sequencing data and genomics data. We reported the different gut microbiota characteristics between MDD and control groups in the Chinese group and further constructed the association between host genetics and the gut microbiome. Actinobacteria and Pseudomonades were found more in the MDD group. We found significant differences in the ACE and Chao indexes of alpha diversity while no discrepancy in beta diversity. We found three associations between host genetics with microbiome features: beta diversity and rs6108 (p = 8.65 × 10–9), Actinobacteria and rs77379751 (p = 8.56 × 10–9), and PWY-5913 and rs1775633082 (p = 4.54 × 10–8). A species of the Romboutsia genus was co-associated with the species of Ruminococcus gnavus in an internetwork through four genes: METTL8, ITGB2, OTULIN, and PROSER3, with a strict threshold (p < 5 × 10–4). Furthermore, our findings suggested that the gut microbiome diversity might affect microRNA expression in the brain and influenced SERPINA5 and other spatially close genes afterward. These findings suggest new linkages between depression and gut microbiome in Asian, Chinese people, which might be mediated by genes and microRNA regulation in space distance.
Background Nonalcoholic fatty liver disease (NAFLD) is a disorder that extends from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), which is effectively alleviated by lifestyle intervention. Nevertheless, DNA methylation mechanism underling the effect of environmental factors on NAFLD and NASH is still obscure. The aim of this study was to investigate the effect of exercise and diet intervention in NAFLD and NASH via DNA methylation of GAB2. Methods Methylation of genomic DNA in human NAFLD was quantified using Infinium Methylation EPIC BeadChip assay after exercise (Ex), low carbohydrate diet (LCD) and exercise plus low carbohydrate diet (ELCD) intervention. The output Idat files were processed using ChAMP package. False discovery rate on genome-wide analysis of DNA methylation (q < 0.05), and cytosine-guanine dinucleotides (CpGs) which are located in promoters were used for subsequent analysis (|Δβ|≥ 0.1). K-means clustering was used to cluster differentially methylated genes according to 3D genome information from Human embryonic stem cell. To quantify DNA methylation and mRNA expression of GRB2 associated binding protein 2 (GAB2) in NASH mice after Ex, low fat diet (LFD) and exercise plus low fat diet (ELFD), MassARRAY EpiTYPER and quantitative reverse transcription polymerase chain reaction were used. Results Both LCD and ELCD intervention on human NAFLD can induce same DNA methylation alterations at critical genes in blood, e.g., GAB2, which was also validated in liver and adipose of NASH mice after LFD and ELFD intervention. Moreover, methylation of CpG units (i.e., CpG_10.11.12) inversely correlated with mRNA expression GAB2 in adipose tissue of NASH mice after ELFD intervention. Conclusions We highlighted the susceptibility of DNA methylation in GAB2 to ELFD intervention, through which exercise and diet can protect against the progression of NAFLD and NASH on the genome level, and demonstrated that the DNA methylation variation in blood could mirror epigenetic signatures in target tissues of important biological function, i.e., liver and adipose tissue. Trialregistration International Standard Randomized Controlled Trial Number Register (ISRCTN42622771)
Objective: This study aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of PCSK1 (proprotein convertase subtilisin/kexin type 1) related to obesity and nonalcoholic fatty liver disease (NAFLD).Methods: In this case-control observational study, four candidate SNPs (rs6234, rs155971, rs6232, rs3811951) of PCSK1 were genotyped in 732 NAFLD patients and 823 healthy control participants, all of whom were of ethnic Han Chinese descent. All participants came from Shanghai, China, and joined our study during 2015 to 2016. The frequencies of each allele and genotype, paired linkage disequilibrium, and haplotype were calculated on the SHEsis platform. In addition to SHEsis, five different genetic models (codominant, dominant, recessive, overdominant, and log-additive) were employed to identify the correlation between genotype frequency and NAFLD. This study was approved by the Medical Ethics Committee of Shanghai University of Traditional Chinese Medicine on December 18, 2017 (approved No. 2017LCSY069).Results: In a comparison of NAFLD patients and healthy participants, none of the four PCSK1 SNPs were significantly correlated with the occurrence of NAFLD (P > 0.05), in either genotypic or allelic distribution. The recessive model of rs3811951 appeared to show a correlation (odds ratio = 1.077; 95% confidence interval = 0.924-1.256; P = 0.04), but there was no statistical significance after Bonferroni correction (P corr > 0.0125).Conclusions: Four obesity-related PCSK1 SNPs (rs6234, rs155971, rs6232, rs3811951) showed no significant correlation with the development of NAFLD in a Han Chinese population.
DiGeorge Syndrome Critical Region Gene 8 (DGCR8) is a key component of the microprocessor complex governing the maturation of most microRNAs, some of which participate in schizophrenia and neural development. Previous studies have found that the 22q11.2 locus, containing DGCR8, confers a risk of schizophrenia. However, the role of DGCR8 in schizophrenia and the early stage of neural development has remained unknown. In the present study, we try to identify the role of DGCR8 in schizophrenia from human samples and animal models. We found that the G allele and GG genotype of rs3757 in DGCR8 conferred a higher risk of schizophrenia, which likely resulted from higher expression of DGCR8 according to our test of dual-luciferase reporter system. Employed overexpression model in utero and adult mice, we also revealed that the aberrant increase of Dgcr8 delayed neuronal migration during embryological development and consequently triggered abnormal behaviors in adult mice. Together, these results demonstrate that DGCR8 may play a role in the etiology of schizophrenia through regulating neural development.
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