ArticlePLoS genetics2014
Regulation of gene expression in autoimmune disease loci and the genetic basis of proliferation in CD4+ effector memory T cells.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 59 citations in OpenAlex.
- Artificial intelligence-driven therapeutics for disease modification in type 1 diabetes: a digital public health and clinical translation framework.Frontiers in public health · 2026Review
- Non-coding autoimmune risk variant defines role for ICOS in T peripheral helper cell development.Nature communications · 2024Article
- Methods and Insights from Single-Cell Expression Quantitative Trait Loci.Annual review of genomics and human genetics · 2023Review
- Expression of Non-T Cell Activation Linker (NTAL) in Jurkat Cells Negatively Regulates TCR Signaling: Potential Role in Rheumatoid Arthritis.International journal of molecular sciences · 2023Article
- Single-cell RNA-sequencing of peripheral blood mononuclear cells reveals widespread, context-specific gene expression regulation upon pathogenic exposure.Nature communications · 2022Article
- Epigenome-wide association study and network analysis for IgA Nephropathy from CD19Epigenetics · 2021Article
- Quantifying the contribution of Neanderthal introgression to the heritability of complex traits.Nature communications · 2021Article
- Human intelectin-1 (ITLN1) genetic variation and intestinal expression.Scientific reports · 2021Article
- The impact of cell type and context-dependent regulatory variants on human immune traits.Genome biology · 2021Article
- CSF-resident CD4Brain communications · 2021Article
- The immunology of rheumatoid arthritis.Nature immunology · 2021Review
- Genomic profiling of T-cell activation suggests increased sensitivity of memory T cells to CD28 costimulation.Genes and immunity · 2020Article
- Multiple sclerosis risk variants regulate gene expression in innate and adaptive immune cells.Life science alliance · 2020Article
- Lymphocyte DNA methylation mediates genetic risk at shared immune-mediated disease loci.The Journal of allergy and clinical immunology · 2020Article
- Allele-specific expression changes dynamically during T cell activation in HLA and other autoimmune loci.Nature genetics · 2020Article
- Leveraging molecular quantitative trait loci to understand the genetic architecture of diseases and complex traits.Nature genetics · 2018Article
- CD4+ and B Lymphocyte Expression Quantitative Traits at Rheumatoid Arthritis Risk Loci in Patients With Untreated Early Arthritis: Implications for Causal Gene Identification.Arthritis & rheumatology (Hoboken, N.J.) · 2018Article
- Thinking BIG rheumatology: how to make functional genomics data work for you.Arthritis research & therapy · 2018Review
- Review
- Profiling RNA-Seq at multiple resolutions markedly increases the number of causal eQTLs in autoimmune disease.PLoS genetics · 2017Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Genome-wide association studies (GWAS) and subsequent dense-genotyping of associated loci identified over a hundred single-nucleotide polymorphism (SNP) variants associated with the risk of rheumatoid arthritis (RA), type 1 diabetes (T1D), and celiac disease (CeD). Immunological and genetic studies suggest a role for CD4-positive effector memory T (CD+ TEM) cells in the pathogenesis of these diseases. To elucidate mechanisms of autoimmune disease alleles, we investigated molecular phenotypes in CD4+ effector memory T cells potentially affected by these variants. In a cohort of genotyped healthy individuals, we isolated high purity CD4+ TEM cells from peripheral blood, then assayed relative abundance, proliferation upon T cell receptor (TCR) stimulation, and the transcription of 215 genes within disease loci before and after stimulation. We identified 46 genes regulated by cis-acting expression quantitative trait loci (eQTL), the majority of which we detected in stimulated cells. Eleven of the 46 genes with eQTLs were previously undetected in peripheral blood mononuclear cells. Of 96 risk alleles of RA, T1D, and/or CeD in densely genotyped loci, eleven overlapped cis-eQTLs, of which five alleles completely explained the respective signals. A non-coding variant, rs389862A, increased proliferative response (p=4.75 × 10-8). In addition, baseline expression of seventeen genes in resting cells reliably predicted proliferative response after TCR stimulation. Strikingly, however, there was no evidence that risk alleles modulated CD4+ TEM abundance or proliferation. Our study underscores the power of examining molecular phenotypes in relevant cells and conditions for understanding pathogenic mechanisms of disease variants.
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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.