rs75932628

This is a protein-altering variant in the TREM2 gene.

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GWAS Catalog Trait Associations (5)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

soluble triggering receptor expressed on myeloid cells 2 measurement

Loya H et al. “A scalable variational inference approach for increased mixed-model association power.” Nature Genetics 57(2):461-468 (2025)

Allele T

OR 1.01

p 3.0e-113

N 47,745

Large GWAS

European

Wang L et al. “Proteo-genomics of soluble TREM2 in cerebrospinal fluid provides novel insights and identifies novel modulators for Alzheimer's disease.” Molecular Neurodegeneration 19(1):1 (2024)

Allele T

OR 1.35

p 7.0e-19

N 3,600

Large GWAS

European

Alzheimer disease

Bellenguez C et al. “New insights into the genetic etiology of Alzheimer's disease and related dementias.” Nature Genetics 54(4):412-436 (2022)

Allele T

OR 2.39

p 3.0e-37

N 487,511

Large GWAS

European

Dalmasso MC et al. “The first genome-wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease.” Alzheimer's & Dementia : the Journal of the Alzheimer's Association 20(2):1298-1308 (2024)

Allele T

OR 2.43

p 5.0e-28

N 488,904

Large GWAS

multi-ancestry

Rajabli F et al. “Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.” Genome Biology 26(1):210 (2025)

Allele T

OR 1.44

p 2.0e-12

N 56,241

Meta-analysisLarge GWAS

multi-ancestry

Jonsson T et al. “Variant of TREM2 associated with the risk of Alzheimer's disease.” The New England Journal of Medicine 368(2):107-16 (2013)

Allele T

OR 2.90

p 2.0e-12

N 12,438

Large GWAS

European

late-onset Alzheimers disease

Sims R et al. “Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.” Nature Genetics 49(9):1373-1384 (2017)

Allele T

OR 2.46

p 5.0e-24

N 34,174

Large GWAS

European

age of onset of Alzheimer disease

Li YJ et al. “Identification of novel genes for age-at-onset of Alzheimer's disease by combining quantitative and survival trait analyses.” Alzheimer's & Dementia : the Journal of the Alzheimer's Association 19(7):3148-3157 (2023)

Allele T

OR 1.07

p 1.0e-13

N 19,564

Large GWAS

European

Alzheimer disease, APOE carrier status

Allele T

OR 1.10

p 2.0e-11

N 56,241

Meta-analysisLarge GWAS

multi-ancestry

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ClinVar annotation

Uncertain Significance★☆☆☆

2 submitters2 publications

TREM2-related disorder

View on ClinVar →

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Research that mentions this SNP (3)

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Mutations inTREM2lead to pure early-onset dementia without bone cysts

ReviewEliane Chouery et al.(2008)· Human Mutation

This is a Master's thesis review of TREM-2 (Triggering Receptor Expressed on Myeloid Cells-2) and its role in neurodegeneration, focusing on Alzheimer's disease and Multiple Sclerosis. The paper discusses how TREM-2 mutations, particularly the R47H variant at rs75932628 (OR=2.92 in Iceland), are associated with increased risk of late-onset Alzheimer's disease, and how TREM-2 expressing microglia regulate inflammatory responses in neurodegenerative diseases.

Traits studied:Alzheimer's diseaseFrontotemporal dementiaMultiple SclerosisNasu-Hakola diseaseParkinson's disease

PubMed DOI Metascience Observatory

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A novel presenilin 1 mutation associated with Pick's disease but not β‐amyloid plaques

ReviewBart Dermaut et al.(2004)· Annals of Neurology

A systematic review of genetic, neuroimaging, and fluid biomarkers for frontotemporal dementia (FTD) across Latin American countries, analyzing 21 studies. The review identified key genetic mutations in C9orf72, GRN, MAPT, TREM2, TARDBP, and PSN-1 genes associated with FTD in LAC populations, including specific variants such as MAPT p.P301L and TREM2 p.W198X.

Traits studied:Behavioral variant FTDFrontotemporal dementiaNonfluent variant PPASemantic variant PPA

PubMed DOI Metascience Observatory

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Atypical dementia associated with a novel presenilin‐2 mutation

ReviewGiuliano Binetti et al.(2003)· Annals of Neurology

A review article examining the role of FDG PET neuroimaging as a preclinical biomarker for dementia in relation to genetic susceptibility. The paper discusses key genetic factors in Alzheimer's disease (APOE ε4 allele with 35-fold increased risk for homozygotes, TREM2 rs75932628, APP A673T) and frontotemporal dementia, showing that FDG PET glucose metabolism reductions precede clinical diagnosis and structural brain changes in presymptomatic carriers of pathogenic mutations and genetic risk variants.

Traits studied:Alzheimer's diseaseDementiaEarly-onset Alzheimer's disease (EOAD)Familial Alzheimer's disease (FAD)Frontotemporal dementia (FTD)Late-onset Alzheimer's disease (LOAD)Mild cognitive impairment (MCI)

PubMed DOI Metascience Observatory

About TREM2

This gene encodes a membrane protein that forms a receptor signaling complex with the TYRO protein tyrosine kinase binding protein. The encoded protein functions in immune response and may be involved in chronic inflammation by triggering the production of constitutive inflammatory cytokines. Defects in this gene are a cause of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

rs75932628

GWAS Catalog Trait Associations (5)

soluble triggering receptor expressed on myeloid cells 2 measurement

Alzheimer disease

late-onset Alzheimers disease

age of onset of Alzheimer disease

Alzheimer disease, APOE carrier status

ClinVar annotation

Research that mentions this SNP (3)

About TREM2

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