ArticleNeurobiology of aging2016
Mutation analysis of the MS4A and TREM gene clusters in a case-control Alzheimer's disease data set.
Article in Neurobiology of aging, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Targeting TREM2 for Parkinson's Disease: Where to Go?Frontiers in immunology · 2021Pooled it
- Interplay between CD33 and TREM2 in Alzheimer's Disease: Potential Mechanistic Insights into Microglial Function in Amyloid Pathology.ACS chemical neuroscience · 2026Review
- Review
- TREML2 enhances sensitivity of acute myeloid leukemia cells to chemotherapy by inhibiting the NF-κB/CXCL10 pathway.Blood science (Baltimore, Md.) · 2025Article
- TREM2 and sTREM2 in Alzheimer's disease: from mechanisms to therapies.Molecular neurodegeneration · 2025Review
- Predicting the impact of missense mutations on an unresolved protein's stability, structure, and function: A case study of Alzheimer's disease-associated TREM2 R47H variant.Computational and structural biotechnology journal · 2025Article
- Biophysical characterization of TREM2 missense variants implicated in neurodegenerative disease.Computational and structural biotechnology journal · 2025Article
- A Risk Variant rs6922617 in TREM Is Discrepantly Associated With Defining Neuropathological Hallmarks in the Alzheimer's Continuum.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- Targeting neuroinflammation in Alzheimer's disease: from mechanisms to clinical applications.Neural regeneration research · 2023Review
- Challenge accepted: uncovering the role of rare genetic variants in Alzheimer's disease.Molecular neurodegeneration · 2022Review
- Alternative Splicing Regulation of Low-Frequency Genetic Variants in Exon 2 ofInternational journal of molecular sciences · 2021Article
- Protective genes and pathways in Alzheimer's disease: moving towards precision interventions.Molecular neurodegeneration · 2021Review
- The most prevalent rare coding variants of TREM2 conferring risk of Alzheimer's disease: A systematic review and meta-analysis.Experimental and therapeutic medicine · 2021Article
- Article
- Potential Bidirectional Relationship Between Periodontitis and Alzheimer's Disease.Frontiers in physiology · 2020Review
- TREM2 brain transcript-specific studies in AD and TREM2 mutation carriers.Molecular neurodegeneration · 2019Article
- Benefits and Challenges of Rare Genetic Variation in Alzheimer's Disease.Current genetic medicine reports · 2019Article
- Protective Variants in Alzheimer's Disease.Current genetic medicine reports · 2019Article
- Myeloid cell-like transcript 2 is related to liver inflammation and the pathogenesis of hepatitis B via the involvement of CD8Clinical and experimental medicine · 2019Article
- New insights into the role of TREM2 in Alzheimer's disease.Molecular neurodegeneration · 2018Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Genome wide association studies have identified an association between Alzheimer's disease (AD) and common polymorphisms in the MS4A and TREM loci (each containing a cluster of homologous genes) and should be thoroughly investigated for the presence of potentially functional variations. We conducted a mutation analysis by next generation sequencing of 15 genes within the MS4A and TREM gene clusters; and catalogued rare coding variants detected in a North American data set of 210 cases and 233 controls. Investigation of the 5 homologues genes in the TREM locus revealed potentially damaging rare variants in TREM2, TREML1, TREML2, and TREML4. In agreement with a previous report, we observed a significant enrichment of TREM2-damaging missense substitutions in cases (N = 9; 4.2%) compared with controls (N=2; 0.9%; p = 0.010; after Yates' correction p = 0.022). Among known AD-associated TREM2 substitutions, we detected p.R47H, p.D87N, and p.H157Y affecting both TREM2 isoforms (NM_018965 and NM_001271821). In addition, we identified 2 cases with novel TREM2 variants (p.L205P and p.G219C), which mapped only to the isoform NM_001271821 at the C-terminus. Investigation of the MS4A gene cluster revealed that potentially damaging missense substitutions and loss-of-function variants were twice as frequent in controls (N = 19; 8.2%) than cases (N = 9; 4.3%), generating a nominally significant result (p = 0.047; after Yates' correction p = 0.07). Validation of our observation in large data sets might address the question whether such variants could contribute to the protective effect of the minor alleles of Genome wide association study-significant single nucleotide polymorphisms at the MS4A locus.
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