ArticleHuman molecular genetics2015
Layered genetic control of DNA methylation and gene expression: a locus of multiple sclerosis in healthy individuals.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- The IMAGEN study: a decade of imaging genetics in adolescents.Molecular psychiatry · 2020Pooled it
- Inferring cell-type-specific causal gene regulatory networks during human neurogenesis.Genome biology · 2023Article
- Genetic impacts on DNA methylation: research findings and future perspectives.Genome biology · 2021Review
- Epigenomics and transcriptomics of systemic sclerosis CD4+ T cells reveal long-range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci.Genome medicine · 2020Article
- Genome-Wide DNA Methylation Analysis of Mammary Gland Tissues From Chinese Holstein Cows WithFrontiers in genetics · 2020Article
- Correlation Between Smoking and Passive Smoking with Multiple Sclerosis and the Underlying Molecular Mechanisms.Medical science monitor : international medical journal of experimental and clinical research · 2019Review
- DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis.Nature communications · 2018Article
- DNA Methylation: a New Player in Multiple Sclerosis.Molecular neurobiology · 2017Review
- Emerging Role for Methylation in Multiple Sclerosis: Beyond DNA.Trends in molecular medicine · 2017Review
- The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases.Frontiers in immunology · 2017Review
Corrections and comments
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Authors and funding
19 authors at 10 institutions in 7 countries.
Funding
Abstract
DNA methylation may contribute to the etiology of complex genetic disorders through its impact on genome integrity and gene expression; it is modulated by DNA-sequence variants, named methylation quantitative trait loci (meQTLs). Most meQTLs influence methylation of a few CpG dinucleotides within short genomic regions (<3 kb). Here, we identified a layered genetic control of DNA methylation at numerous CpGs across a long 300 kb genomic region. This control involved a single long-range meQTL and multiple local meQTLs. The long-range meQTL explained up to 75% of variance in methylation of CpGs located over extended areas of the 300 kb region. The meQTL was identified in four samples (P = 2.8 × 10(-17), 3.1 × 10(-31), 4.0 × 10(-71) and 5.2 × 10(-199)), comprising a total of 2796 individuals. The long-range meQTL was strongly associated not only with DNA methylation but also with mRNA expression of several genes within the 300 kb region (P = 7.1 × 10(-18)-1.0 × 10(-123)). The associations of the meQTL with gene expression became attenuated when adjusted for DNA methylation (causal inference test: P = 2.4 × 10(-13)-7.1 × 10(-20)), indicating coordinated regulation of DNA methylation and gene expression. Further, the long-range meQTL was found to be in linkage disequilibrium with the most replicated locus of multiple sclerosis, a disease affecting primarily the brain white matter. In middle-aged adults free of the disease, we observed that the risk allele was associated with subtle structural properties of the brain white matter found in multiple sclerosis (P = 0.02). In summary, we identified a long-range meQTL that controls methylation and expression of several genes and may be involved in increasing brain vulnerability to multiple sclerosis.
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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.