ArticleAmerican journal of human genetics2014
A common functional regulatory variant at a type 2 diabetes locus upregulates ARAP1 expression in the pancreatic beta cell.
Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 3 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.Nature genetics · 2018Pooled it
- Heritability and Genome-Wide Association Analyses of Sleep Duration in Children: The EAGLE Consortium.Sleep · 2016Pooled it
- Bridging the variant-to-function gap in type 2 diabetes: advances and challenges.Diabetologia · 2026Review
- Abundant repressor binding sites in human enhancers are associated with the fine-tuning of gene regulation.iScience · 2025Article
- Insulin-related traits and prostate cancer: A Mendelian randomization study.Computational and structural biotechnology journal · 2024Article
- Modeling common and rare genetic risk factors of neuropsychiatric disorders in human induced pluripotent stem cells.Schizophrenia research · 2024Review
- Heterogeneous enhancer states orchestrate β cell responses to metabolic stress.Nature communications · 2024Article
- Article
- Multiple genetic variants at the SLC30A8 locus affect local super-enhancer activity and influence pancreatic β-cell survival and function.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- A comprehensive in silico investigation into the pathogenic SNPs in the RTEL1 gene and their biological consequences.PloS one · 2024Article
- Multiple genetic variants at thebioRxiv : the preprint server for biology · 2023Article
- Bioinformatics and Next-Generation Data Analysis for Identification of Genes and Molecular Pathways Involved in Subjects with Diabetes and Obesity.Medicina (Kaunas, Lithuania) · 2023Article
- Loci Associated with Negative Heterosis for Viability and Meat Productivity in Interspecific Sheep Hybrids.Animals : an open access journal from MDPI · 2023Article
- Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines.Cell genomics · 2022Article
- Deep Resequencing of 9 Candidate Genes Identifies a Role for ARAP1 and IGF2BP2 in Modulating Insulin Secretion Adjusted for Insulin Resistance in Obese Southern Europeans.International journal of molecular sciences · 2022Article
- Stem Cell-Derived β Cells: A Versatile Research Platform to Interrogate the Genetic Basis of β Cell Dysfunction.International journal of molecular sciences · 2022Review
- Shared Genetic Basis and Causal Relationship Between Television Watching, Breakfast Skipping and Type 2 Diabetes: Evidence From a Comprehensive Genetic Analysis.Frontiers in endocrinology · 2022Article
- Association of prenatal acetaminophen use and acetaminophen metabolites with DNA methylation of newborns: analysis of two consecutive generations of the Isle of Wight birth cohort.Environmental epigenetics · 2022Article
- Identification of direct transcriptional targets of NFATC2 that promote β cell proliferation.The Journal of clinical investigation · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Genome-wide association studies (GWASs) have identified more than 70 loci associated with type 2 diabetes (T2D), but for most, the underlying causal variants, associated genes, and functional mechanisms remain unknown. At a T2D- and fasting-proinsulin-associated locus on 11q13.4, we have identified a functional regulatory DNA variant, a candidate target gene, and a plausible underlying molecular mechanism. Fine mapping, conditional analyses, and exome array genotyping in 8,635 individuals from the Metabolic Syndrome in Men study confirmed a single major association signal between fasting proinsulin and noncoding variants (p = 7.4 × 10(-50)). Measurement of allele-specific mRNA levels in human pancreatic islet samples heterozygous for rs11603334 showed that the T2D-risk and proinsulin-decreasing allele (C) is associated with increased ARAP1 expression (p < 0.02). We evaluated four candidate functional SNPs for allelic effects on transcriptional activity by performing reporter assays in rodent pancreatic beta cell lines. The C allele of rs11603334, located near one of the ARAP1 promoters, exhibited 2-fold higher transcriptional activity than did the T allele (p < 0.0001); three other candidate SNPs showed no allelic differences. Electrophoretic mobility shift assays demonstrated decreased binding of pancreatic beta cell transcriptional regulators PAX6 and PAX4 to the rs11603334 C allele. Collectively, these data suggest that the T2D-risk allele of rs11603334 could abrogate binding of a complex containing PAX6 and PAX4 and thus lead to increased promoter activity and ARAP1 expression in human pancreatic islets. This work suggests that increased ARAP1 expression might contribute to T2D susceptibility at this GWAS locus.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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 OpenQuestion graph.