ArticleAmerican journal of human genetics2023
High-throughput functional dissection of noncoding SNPs with biased allelic enhancer activity for insulin resistance-relevant phenotypes.
Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Linking Iris Cis-Regulatory Variants to Primary Angle-Closure Glaucoma Via Clinical Imaging and Multiomics.Investigative ophthalmology & visual science · 2024Pooled it
- Genomic language model for predicting enhancers and their allele-specific activity in the human genome.Bioinformatics (Oxford, England) · 2026Article
- Segmentally Duplicated Regulatory Elements Undergo Human-Specific Rewiring.Molecular biology and evolution · 2026Article
- Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate causal variants in macular degeneration.Cell reports · 2026Article
- Segmentally duplicated regulatory elements undergo human-specific rewiring.bioRxiv : the preprint server for biology · 2025Article
- Analysis of biased allelic enhancer activity of schizophrenia-linked common variants.Communications biology · 2025Article
- Variant-to-function approaches for adipose tissue: Insights into cardiometabolic disorders.Cell genomics · 2025Review
- HDI-STARR-seq: Condition-specific enhancer discovery in mouse liver in vivo.BMC genomics · 2024Article
- Review
- HDI-STARR-seq: Condition-specific enhancer discovery in mouse liver in vivo.bioRxiv : the preprint server for biology · 2024Article
- Constructing eRNA-mediated gene regulatory networks to explore the genetic basis of muscle and fat-relevant traits in pigs.Genetics, selection, evolution : GSE · 2024Article
- Integrative high-throughput enhancer surveying and functional verification divulges a YY2-condensed regulatory axis conferring risk for osteoporosis.Cell genomics · 2024Article
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Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most of the single-nucleotide polymorphisms (SNPs) associated with insulin resistance (IR)-relevant phenotypes by genome-wide association studies (GWASs) are located in noncoding regions, complicating their functional interpretation. Here, we utilized an adapted STARR-seq to evaluate the regulatory activities of 5,987 noncoding SNPs associated with IR-relevant phenotypes. We identified 876 SNPs with biased allelic enhancer activity effects (baaSNPs) across 133 loci in three IR-relevant cell lines (HepG2, preadipocyte, and A673), which showed pervasive cell specificity and significant enrichment for cell-specific open chromatin regions or enhancer-indicative markers (H3K4me1, H3K27ac). Further functional characterization suggested several transcription factors (TFs) with preferential allelic binding to baaSNPs. We also incorporated multi-omics data to prioritize 102 candidate regulatory target genes for baaSNPs and revealed prevalent long-range regulatory effects and cell-specific IR-relevant biological functional enrichment on them. Specifically, we experimentally verified the distal regulatory mechanism at IRS1 locus, in which rs952227-A reinforces IRS1 expression by long-range chromatin interaction and preferential binding to the transcription factor HOXC6 to augment the enhancer activity. Finally, based on our STARR-seq screening data, we predicted the enhancer activity of 227,343 noncoding SNPs associated with IR-relevant phenotypes (fasting insulin adjusted for BMI, HDL cholesterol, and triglycerides) from the largest available GWAS summary statistics. We further provided an open resource (http://www.bigc.online/fnSNP-IR) for better understanding genetic regulatory mechanisms of IR-relevant phenotypes.
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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.