A Replication Study Identified Seven SNPs Associated with Quantitative Traits of Type 2 Diabetes among Chinese Population in A Cross-Sectional Study

Yuan, Fan; Li, Hui; Song, Chao; Fang, Hongyun; Wang, Rui; Zhang, Yan; Gong, Wei; Liu, Ailing

doi:10.3390/ijerph17072439

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…RAS guanyl nucleotide-releasing protein (RASGRP) functions as a diacylglycerol DAG-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. Although the genetic variants associated with RASGRP1 have been linked to both T1D and T2D 62 , 63 , the role of RASGRP1 in human β cells is largely unknown. Here, we found that loss of RASGRP1 , knockout of the regulatory region of RASGRP1, and risk allele of rs55728265 leads to increased β cell death.…”

Section: Discussionmentioning

confidence: 99%

An integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D associated genes and regulatory signals

Chen,

Zhao,

Albanus

et al. 2023

Preprint

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Genome wide association studies (GWAS) have identified over 100 signals associated with type 1 diabetes (T1D). However, translating any given T1D GWAS signal into mechanistic insights, such as causal variants, their target genes, and the specific cell types involved, has been challenging. Here, we present a comprehensive multi-omic integrative analysis of single-cell/nucleus resolution profiles of gene expression and chromatin accessibility in healthy and autoantibody+ (AAB+) human pancreatic islets, and islets under T1D-stimulating conditions. We nominate effector cell types for all T1D GWAS signals and the regulatory elements and genes for three independent T1D risk variants acting through β cells at the DLK1/MEG3, RASGRP1, and TOX loci. Subsequently, we validated the functional impact of these genes and regulatory regions using isogenic human embryonic stem cells (hESCs) and found that loss of RASGRP1 or DLK1, as well as disruption of their regulatory regions, led to increased β cell apoptosis. Furthermore, β cells derived from isogenic hESCs carrying the T1D risk allele of rs3783355 associated with DLK1 showed elevated β cell death. Through RNA-seq and ATAC-seq analyses, we identified five genes upregulated in both RASGRP1-/- and DLK1-/- β-like cells, four of which are associated with T1D. This integrative approach combining single-cell multi-omics, GWAS, and isogenic hPSC-derived β-like cells illuminates cell type context, genes, single nucleotide polymorphisms (SNPs), and regulatory elements underlying T1D-associated signals, providing insights into the biological functions and molecular mechanisms involved.

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Section: Discussionmentioning

confidence: 99%

An integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D associated genes and regulatory signals

Chen,

Zhao,

Albanus

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…MAEA is a membrane-associated E3 ubiquitin ligase subunit that is essential for the maintenance of hematopoietic stem cells and lymphatic potential; deletion of MAEA increases the expression of surface cytokine receptors in hematopoietic stem cells and impairs autophagy flux [ 100 ]. MAEA overexpression in primary mouse liver cells attenuates hepatic gluconeogenesis and reduces the risk of insulin resistance, which may improve type 2 diabetes mellitus [ 101 , 102 ]. MAEA is associated with low bone mineral density in postmenopausal women [ 103 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Regulatory Factors and Prognostic Markers in Amyotrophic Lateral Sclerosis

Sun

et al. 2022

Antioxidants

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of motor neurons, leading to muscle atrophy, paralysis and even death. Immune disorder, redox imbalance, autophagy disorder, and iron homeostasis disorder have been shown to play critical roles in the pathogenesis of ALS. However, the exact pathogenic genes and the underlying mechanism of ALS remain unclear. The purpose of this study was to screen for pathogenic regulatory genes and prognostic markers in ALS using bioinformatics methods. We used Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, gene set enrichment analysis (GSEA), and expression regulation network analysis to investigate the function of differentially expressed genes in the nerve tissue, lymphoid tissue, and whole blood of patients with ALS. Our results showed that the up-regulated genes were mainly involved in immune regulation and inflammation, and the down-regulated genes were mainly involved in energy metabolism and redox processes. Eleven up-regulated transcription factors (CEBPB, CEBPD, STAT5A, STAT6, RUNX1, REL, SMAD3, GABPB2, FOXO1, PAX6, and FOXJ1) and one down-regulated transcription factor (NOG) in the nerve tissue of patients with ALS likely play important regulatory roles in the pathogenesis of ALS. Based on construction and evaluation of the ALS biomarker screening model, cluster analysis of the identified characteristic genes, univariate Cox proportional hazards regression analysis, and the random survival forest algorithm, we found that MAEA, TPST1, IFNGR2, and ALAS2 may be prognostic markers regarding the survival of ALS patients. High expression of MAEA, TPST1, and IFNGR2 and low expression of ALAS2 in ALS patients may be closely related to short survival of ALS patients. Taken together, our results indicate that immune disorders, inflammation, energy metabolism, and redox imbalance may be the important pathogenic factors of ALS. CEBPB, CEBPD, STAT5A, STAT6, RUNX1, REL, SMAD3, GABPB2, FOXO1, PAX6, FOXJ1, and NOG may be important regulatory factors linked to the pathogenesis of ALS. MAEA, TPST1, IFNGR2, and ALAS2 are potential important ALS prognostic markers. Our findings provide evidence on the pathogenesis of ALS, potential targets for the development of new drugs for ALS, and important markers for predicting ALS prognosis.

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Synergism of cell adhesion regulatory genes and instant air pollutants on blood pressure elevation

Wang

Peng

et al. 2023

Chemosphere

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A Replication Study Identified Seven SNPs Associated with Quantitative Traits of Type 2 Diabetes among Chinese Population in A Cross-Sectional Study

Cited by 3 publications

References 35 publications

An integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D associated genes and regulatory signals

An integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D associated genes and regulatory signals

Identification of Regulatory Factors and Prognostic Markers in Amyotrophic Lateral Sclerosis

Synergism of cell adhesion regulatory genes and instant air pollutants on blood pressure elevation

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