SynthesisPLoS medicine2018
Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies.
Synthesis in PLoS medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 94 papers.
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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.
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Who cites it
94 citing papers in PubMed, 194 citations in OpenAlex.
- The Impact of Antigen Presentation on BBB Disruption and Neuroinflammation.Physiology (Bethesda, Md.) · 2026Review
- Sex-aware causal inference assessment of the immune system in complex neurodegenerative diseases.Brain : a journal of neurology · 2026Article
- Novel Alzheimer's disease-associated variants and genetic interactions identified from UK biobank whole-exome sequencing data using IBI-DT.Scientific reports · 2026Article
- Shared Neuroinflammatory Mechanisms Across Dementia Types: An Integrative Review.International journal of molecular sciences · 2025Review
- Update on Disease-Modifying Pharmacological Treatments for Frontotemporal Dementia (FTD): A Scoping Review of Registered Trials.NeuroSci · 2025Review
- Genetic insights into the association between inflammatory bowel disease and Alzheimer's disease.Genes and immunity · 2025Article
- Exploiting pleiotropy to enhance variant discovery with functional false discovery rates.Nature computational science · 2025Article
- Opposing role of phagocytic receptors MERTK and AXL in Progranulin deficient FTD.Communications biology · 2025Article
- Sex differences in the clinical manifestation of autosomal dominant frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Sex differences in the executive and behavioral reserve of autosomal dominant frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Article
- Frontotemporal Dementia Differential Diagnosis in Clinical Practice: A Single-Center Retrospective Review of Frontal Behavioral Referrals.Neurology. Clinical practice · 2025Article
- Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.Brain communications · 2025Article
- Article
- CRISPRi-based screens in iAssembloids to elucidate neuron-glia interactions.bioRxiv : the preprint server for biology · 2024Article
- Gut microbiota immune cross-talk in amyotrophic lateral sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Article
- PET Imaging to Measure Neuroinflammation In Vivo.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Targeting Progranulin as an Immuno-Neurology Therapeutic Approach.International journal of molecular sciences · 2023Review
- Immune cell counts in cerebrospinal fluid predict cognitive function in aging and neurodegenerative disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
30 authors at 12 institutions in 5 countries.
Funding
Abstract
backgroundConverging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed. METHODS AND
findingsUsing large genome-wide association studies (GWASs) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with FTD-related disorders-namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)-and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis. We found up to 270-fold genetic enrichment between FTD and RA, up to 160-fold genetic enrichment between FTD and UC, up to 180-fold genetic enrichment between FTD and T1D, and up to 175-fold genetic enrichment between FTD and CeD. In contrast, for CBD and PSP, only 1 of the 6 immune-mediated diseases produced genetic enrichment comparable to that seen for FTD, with up to 150-fold genetic enrichment between CBD and CeD and up to 180-fold enrichment between PSP and RA. Further, we found minimal enrichment between ALS and the immune-mediated diseases tested, with the highest levels of enrichment between ALS and RA (up to 20-fold). For FTD, at a conjunction false discovery rate < 0.05 and after excluding SNPs in linkage disequilibrium, we found that 8 of the 15 identified loci mapped to the human leukocyte antigen (HLA) region on Chromosome (Chr) 6. We also found novel candidate FTD susceptibility loci within LRRK2 (leucine rich repeat kinase 2), TBKBP1 (TBK1 binding protein 1), and PGBD5 (piggyBac transposable element derived 5). Functionally, we found that the expression of FTD-immune pleiotropic genes (particularly within the HLA region) is altered in postmortem brain tissue from patients with FTD and is enriched in microglia/macrophages compared to other central nervous system cell types. The main study limitation is that the results represent only clinically diagnosed individuals. Also, given the complex interconnectedness of the HLA region, we were not able to define the specific gene or genes on Chr 6 responsible for our pleiotropic signal.
conclusionsWe show immune-mediated genetic enrichment specifically in FTD, particularly within the HLA region. Our genetic results suggest that for a subset of patients, immune dysfunction may contribute to FTD risk. These findings have potential implications for clinical trials targeting immune dysfunction in patients with FTD.
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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.