ArticleAmerican journal of human genetics2012
Genetic risk factors for type 2 diabetes: a trans-regulatory genetic architecture?
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 4 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 4 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- Association ofFrontiers in endocrinology · 2025Pooled it
- Meta- and cross-species analyses of insulin resistance based on gene expression datasets in human white adipose tissues.Scientific reports · 2018Pooled it
- Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs.Scientific reports · 2016Pooled it
- Genetic association signal near NTN4 in Tourette syndrome.Annals of neurology · 2014Pooled it
- Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes.The pharmacogenomics journal · 2018Trial
- Multi-omics analysis identifies SMPD1 as a key contributor in sphingolipid pathway for Type 2 diabetes pathogenesis.Genes & genomics · 2026Article
- Integration of single-cell datasets reveals novel transcriptomic signatures of β-cells in human type 2 diabetes.NAR genomics and bioinformatics · 2020Article
- Expression Profile of SARS-CoV-2 Host Receptors in Human Pancreatic Islets Revealed Upregulation ofBiology · 2020Article
- Weighted Fused Pathway Graphical Lasso for Joint Estimation of Multiple Gene Networks.Frontiers in genetics · 2019Article
- Increased identification of novel variants in type 2 diabetes, birth weight and their pleiotropic loci.Journal of diabetes · 2017Article
- Type 2 diabetes: genetic data sharing to advance complex disease research.Nature reviews. Genetics · 2016Review
- Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin Resistance in Male Mice.Cell reports · 2016Article
- Transcriptomics in type 2 diabetes: Bridging the gap between genotype and phenotype.Genomics data · 2016Article
- Imputing Gene Expression in Uncollected Tissues Within and Beyond GTEx.American journal of human genetics · 2016Article
- Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.Nature genetics · 2015Article
- Novel Observations From Next-Generation RNA Sequencing of Highly Purified Human Adult and Fetal Islet Cell Subsets.Diabetes · 2015Article
- Genetic control of gene expression at novel and established chronic obstructive pulmonary disease loci.Human molecular genetics · 2015Article
- Increased Transcript Complexity in Genes Associated with Chronic Obstructive Pulmonary Disease.PloS one · 2015Article
- Cross-tissue and tissue-specific eQTLs: partitioning the heritability of a complex trait.American journal of human genetics · 2014Article
- Identification and validation of genetic variants that influence transcription factor and cell signaling protein levels.American journal of human genetics · 2014Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
To date, 68 loci have been associated with type 2 diabetes (T2D) or glucose homeostasis traits. We report here the results of experiments aimed at functionally characterizing the SNPs replicated for T2D and glucose traits. We sought to determine whether these loci were associated with transcript levels in adipose, muscle, liver, lymphocytes, and pancreatic β-cells. We found an excess of trans, rather than cis, associations among these SNPs in comparison to what was expected in adipose and muscle. Among transcripts differentially expressed (FDR < 0.05) between muscle or adipose cells of insulin-sensitive individuals and those of insulin-resistant individuals (matched on BMI), trans-regulated transcripts, in contrast to the cis-regulated ones, were enriched. The paucity of cis associations with transcripts was confirmed in a study of liver transcriptome and was further supported by an analysis of the most detailed transcriptome map of pancreatic β-cells. Relative to location- and allele-frequency-matched random SNPs, both the 68 loci and top T2D-associated SNPs from two large-scale genome-wide studies were enriched for trans eQTLs in adipose and muscle but not in lymphocytes. Our study suggests that T2D SNPs have broad-reaching and tissue-specific effects that often extend beyond local transcripts and raises the question of whether patterns of cis or trans transcript regulation are a key feature of the architecture of complex traits.
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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.