SynthesisDiabetes2022
Recessive Genome-Wide Meta-analysis Illuminates Genetic Architecture of Type 2 Diabetes.
Synthesis in Diabetes, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Genome Wide Association Study (GWAS) Identifies Novel Genetic Loci for Second-Generation Antipsychotics (SGA)-Induced Metabolic Syndrome (MetS).Clinical and translational science · 2025Pooled it
- Type 2 Diabetes Causally Reduces Circulating Vitamin D Levels: A Multi-Ancestry Mendelian Randomization Study.Nutrients · 2026Article
- Genetic Investigation of Corrected QT Interval Sensitivity to Oral Bepridil Hydrochloride Hydrate in Patients With Atrial Fibrillation.Journal of the American Heart Association · 2026Article
- Identification of lipid quantitative trait loci linked with cardiometabolic disease in Asian Indians and Europeans: A genome-wide association study and Mendelian randomization.PLoS medicine · 2026Observational
- Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity.Nature genetics · 2026Article
- Contribution of dominant and recessive model effects to the genetic architecture of Idiopathic Pulmonary Fibrosis.medRxiv : the preprint server for health sciences · 2026Article
- Cost-effective non-additive GWAS across 2329 diseases in 500,349 individuals.Nature communications · 2025Article
- Prediction of human missense variant effects from functional evidence.Research square · 2025Article
- Widespread recessive effects on common diseases in a cohort of 44,000 British Pakistanis and Bangladeshis with high autozygosity.American journal of human genetics · 2025Article
- Genetic determinants and clinical significance of circulating and tumor-specific levels of insulin-like growth factor binding protein 7 (IGFBP7) in a Swedish breast cancer cohort.Carcinogenesis · 2025Article
- Excess of rare noncoding variants in several type 2 diabetes candidate genes among Asian Indian families.Communications medicine · 2025Article
- Shared Genetic Architectures between Coronary Artery Disease and Type 2 Diabetes Mellitus in East Asian and European Populations.Biomedicines · 2024Article
- A polygenic score method boosted by non-additive models.Nature communications · 2024Article
- Statistical inference with large-scale trait imputation.Statistics in medicine · 2024Article
- Exploring the design of clinical research studies on the efficacy mechanisms in type 2 diabetes mellitus.Frontiers in endocrinology · 2024Review
- Article
- Using GWAS summary data to impute traits for genotyped individuals.HGG advances · 2023Article
- FGF20 and PGM2 variants are associated with childhood asthma in family-based whole-genome sequencing studies.Human molecular genetics · 2023Article
- Assessing the prediction of type 2 diabetes risk using polygenic and clinical risk scores in South Asian study populations.Therapeutic advances in endocrinology and metabolism · 2023Article
- The missing heritability in type 1 diabetes.Diabetes, obesity & metabolism · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 6 institutions in 4 countries.
Funding
Abstract
Most genome-wide association studies (GWAS) of complex traits are performed using models with additive allelic effects. Hundreds of loci associated with type 2 diabetes have been identified using this approach. Additive models, however, can miss loci with recessive effects, thereby leaving potentially important genes undiscovered. We conducted the largest GWAS meta-analysis using a recessive model for type 2 diabetes. Our discovery sample included 33,139 case subjects and 279,507 control subjects from 7 European-ancestry cohorts, including the UK Biobank. We identified 51 loci associated with type 2 diabetes, including five variants undetected by prior additive analyses. Two of the five variants had minor allele frequency of <5% and were each associated with more than a doubled risk in homozygous carriers. Using two additional cohorts, FinnGen and a Danish cohort, we replicated three of the variants, including one of the low-frequency variants, rs115018790, which had an odds ratio in homozygous carriers of 2.56 (95% CI 2.05-3.19; P = 1 × 10-16) and a stronger effect in men than in women (for interaction, P = 7 × 10-7). The signal was associated with multiple diabetes-related traits, with homozygous carriers showing a 10% decrease in LDL cholesterol and a 20% increase in triglycerides; colocalization analysis linked this signal to reduced expression of the nearby PELO gene. These results demonstrate that recessive models, when compared with GWAS using the additive approach, can identify novel loci, including large-effect variants with pathophysiological consequences relevant to type 2 diabetes.
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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 Socratic graph.