ArticleAmerican journal of human genetics2023
Genome-wide aggregated trans-effects on risk of type 1 diabetes: A test of the "omnigenic" sparse effector hypothesis of complex trait genetics.
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 10 papers.
What it found
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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.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Functionally informed cis and trans proteome-wide association studies prioritize disease-critical genes.Research square · 2026Article
- Functionally informed cis and trans proteome-wide association studies prioritize disease-critical genes.medRxiv : the preprint server for health sciences · 2026Article
- Interaction BetweenNutrients · 2025Observational
- A combined genomic arrhythmia propensity score delineates cumulative risk.Cell reports. Medicine · 2025Article
- Genome-Wide Aggregated Trans-Effects Analysis Implicates Deficient Type III Interferon Signaling as a Key Cause of Inflammatory Bowel Disease.Inflammatory bowel diseases · 2025Article
- Genome-Wide Aggregated Trans Effects Analysis for Circulating Proteins Indicates a Key Role of Immune Checkpoints in Type 1 Diabetes.Diabetes · 2025Article
- Discovery of core genes for systemic lupus erythematosus via genome-wide aggregated trans-effects analysis.Genes and immunity · 2025Article
- Genome-Wide Aggregated Trans Effects Analysis Identifies Genes Encoding Immune Checkpoints as Core Genes for Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Article
- Genetic predisposition to nephropathy and associated cardiovascular disease in people with type 1 diabetes: role of the angiotensinI-converting enzyme (ACE), and beyond; a narrative review.Cardiovascular diabetology · 2024Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The "omnigenic" hypothesis postulates that the polygenic effects of common SNPs on a typical complex trait are mediated through trans-effects on expression of a relatively sparse set of effector ("core") genes. We tested this hypothesis in a study of 4,964 cases of type 1 diabetes (T1D) and 7,497 controls by using summary statistics to calculate aggregated (excluding the HLA region) trans-scores for gene expression in blood. From associations of T1D with aggregated trans-scores, nine putative core genes were identified, of which three-STAT1, CTLA4 and FOXP3-are genes in which variants cause monogenic forms of autoimmune diabetes. Seven of these genes affect the activity of regulatory T cells, and two are involved in immune responses to microbial lipids. Four T1D-associated genomic regions could be identified as master regulators via trans-effects on gene expression. These results support the sparse effector hypothesis and reshape our understanding of the genetic architecture of T1D.
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Registered trials
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