ArticleNature communications2021
Functional characterization of T2D-associated SNP effects on baseline and ER stress-responsive β cell transcriptional activation.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Massively parallel assessment of gene regulatory activity at human cortical-structure-associated variants.Nature neuroscience · 2026Article
- Multi-tissue analyses of allele-specific chromatin accessibility nominate likely functional variants for type 2 diabetes.medRxiv : the preprint server for health sciences · 2026Article
- Using a modular massively parallel reporter assay to discover context-dependent regulatory activity in type 2 diabetes-linked noncoding regions.HGG advances · 2026Article
- Functional genomics reveals mediators of beta cell survival in ER stress and type 2 diabetes risk.bioRxiv : the preprint server for biology · 2026Article
- Bridging the variant-to-function gap in type 2 diabetes: advances and challenges.Diabetologia · 2026Review
- IP-SNPs-seq links noncoding risk alleles to lineage transcription factor programs in prostate cancer.Cellular and molecular life sciences : CMLS · 2025Article
- Combined SNPs sequencing and allele specific proteomics capture reveal functional causality underpinning the 2p25 prostate cancer susceptibility locus.Nature communications · 2025Article
- Applications of high-throughput reporter assays to gene regulation studies.Current opinion in structural biology · 2025Review
- Article
- Coronary artery disease-associated variants regulate vascular smooth muscle cell gene expression.Nature cardiovascular research · 2025Article
- Update on the genetics of allergic diseases.The Journal of allergy and clinical immunology · 2025Review
- Variant-to-function approaches for adipose tissue: Insights into cardiometabolic disorders.Cell genomics · 2025Review
- Article
- Stress-Related LncRNAs and Their Roles in Diabetes and Diabetic Complications.International journal of molecular sciences · 2025Review
- Comprehensive mapping of genetic variation at Epromoters reveals pleiotropic association with multiple disease traits.Nucleic acids research · 2025Article
- Functional dissection of metabolic trait-associated gene regulation in steady state and stimulated human skeletal muscle cells.bioRxiv : the preprint server for biology · 2025Article
- β-cell heterogeneity and molecular plasticity in type 2 diabetes: multi-omics perspectives and the role of gut microbiota.Frontiers in cell and developmental biology · 2025Review
- Multi-omic human pancreatic islet endoplasmic reticulum and cytokine stress response mapping provides type 2 diabetes genetic insights.Cell metabolism · 2024Article
- Retrotransposons and Diabetes Mellitus.Epigenomes · 2024Review
- Article
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Authors and funding
9 authors.
Funding
Abstract
Genome-wide association studies (GWAS) have linked single nucleotide polymorphisms (SNPs) at >250 loci in the human genome to type 2 diabetes (T2D) risk. For each locus, identifying the functional variant(s) among multiple SNPs in high linkage disequilibrium is critical to understand molecular mechanisms underlying T2D genetic risk. Using massively parallel reporter assays (MPRA), we test the cis-regulatory effects of SNPs associated with T2D and altered in vivo islet chromatin accessibility in MIN6 β cells under steady state and pathophysiologic endoplasmic reticulum (ER) stress conditions. We identify 1,982/6,621 (29.9%) SNP-containing elements that activate transcription in MIN6 and 879 SNP alleles that modulate MPRA activity. Multiple T2D-associated SNPs alter the activity of short interspersed nuclear element (SINE)-containing elements that are strongly induced by ER stress. We identify 220 functional variants at 104 T2D association signals, narrowing 54 signals to a single candidate SNP. Together, this study identifies elements driving β cell steady state and ER stress-responsive transcriptional activation, nominates causal T2D SNPs, and uncovers potential roles for repetitive elements in β cell transcriptional stress response and T2D genetics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.