SynthesisPLoS genetics2010
Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits.
Synthesis in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 305 papers, 31 of them syntheses 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
305 citing papers in PubMed, 31 syntheses or guidelines pooled it, 481 citations in OpenAlex.
- Alcohol use disorder is associated with DNA methylation-based shortening of telomere length and regulated by TESPA1: implications for aging.Molecular psychiatry · 2022Pooled it
- Gene Set Enrichment Analsyes Identify Pathways Involved in Genetic Risk for Diabetic Retinopathy.American journal of ophthalmology · 2022Pooled it
- Genetic factors influencing a neurobiological substrate for psychiatric disorders.Translational psychiatry · 2021Pooled it
- A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.Communications biology · 2021Pooled it
- Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia.Nature genetics · 2020Pooled it
- GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI.Science advances · 2019Pooled it
- Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.Nature genetics · 2019Pooled it
- Discovery of common and rare genetic risk variants for colorectal cancer.Nature genetics · 2019Pooled it
- Genome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci.Human molecular genetics · 2018Pooled it
- Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.Nature genetics · 2018Pooled it
- Multi-ethnic genome-wide association study for atrial fibrillation.Nature genetics · 2018Pooled it
- Locus and gene-based GWAS meta-analysis identifies new diabetic nephropathy genes.Immunogenetics · 2018Pooled it
- Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma.Nature genetics · 2018Pooled it
- Common and Rare Coding Genetic Variation Underlying the Electrocardiographic PR Interval.Circulation. Genomic and precision medicine · 2018Pooled it
- Genome-Wide Meta-Analysis Unravels Interactions between Magnesium Homeostasis and Metabolic Phenotypes.Journal of the American Society of Nephrology : JASN · 2018Pooled it
- Meta-analysis of genome-wide SNP- and pathway-based associations for facets of neuroticism.Journal of human genetics · 2017Pooled it
- Genome-wide association study identifies 112 new loci for body mass index in the Japanese population.Nature genetics · 2017Pooled it
- Pathways to smoking behaviours: biological insights from the Tobacco and Genetics Consortium meta-analysis.Molecular psychiatry · 2017Pooled it
- Pooled it
- Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans.Human molecular genetics · 2016Pooled it
245 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial dysfunction has been observed in skeletal muscle of people with diabetes and insulin-resistant individuals. Furthermore, inherited mutations in mitochondrial DNA can cause a rare form of diabetes. However, it is unclear whether mitochondrial dysfunction is a primary cause of the common form of diabetes. To date, common genetic variants robustly associated with type 2 diabetes (T2D) are not known to affect mitochondrial function. One possibility is that multiple mitochondrial genes contain modest genetic effects that collectively influence T2D risk. To test this hypothesis we developed a method named Meta-Analysis Gene-set Enrichment of variaNT Associations (MAGENTA; http://www.broadinstitute.org/mpg/magenta). MAGENTA, in analogy to Gene Set Enrichment Analysis, tests whether sets of functionally related genes are enriched for associations with a polygenic disease or trait. MAGENTA was specifically designed to exploit the statistical power of large genome-wide association (GWA) study meta-analyses whose individual genotypes are not available. This is achieved by combining variant association p-values into gene scores and then correcting for confounders, such as gene size, variant number, and linkage disequilibrium properties. Using simulations, we determined the range of parameters for which MAGENTA can detect associations likely missed by single-marker analysis. We verified MAGENTA's performance on empirical data by identifying known relevant pathways in lipid and lipoprotein GWA meta-analyses. We then tested our mitochondrial hypothesis by applying MAGENTA to three gene sets: nuclear regulators of mitochondrial genes, oxidative phosphorylation genes, and approximately 1,000 nuclear-encoded mitochondrial genes. The analysis was performed using the most recent T2D GWA meta-analysis of 47,117 people and meta-analyses of seven diabetes-related glycemic traits (up to 46,186 non-diabetic individuals). This well-powered analysis found no significant enrichment of associations to T2D or any of the glycemic traits in any of the gene sets tested. These results suggest that common variants affecting nuclear-encoded mitochondrial genes have at most a small genetic contribution to T2D susceptibility.
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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.