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rs75932628

From SNPedia

Orientationplus
Stabilizedplus
Geno Mag Summary
(C;C) 0 common in clinvar
(C;T) 3 risk of Alzheimer's disease
(T;T) 3.5 risk of Alzheimer's disease
ReferenceGRCh38 38.1/141
Chromosome6
Position41161514
GeneLOC105375056, TREM2
is asnp
is mentioned by
dbSNPrs75932628
ClinGenrs75932628
ebirs75932628
HLIrs75932628
Exacrs75932628
Varsomers75932628
Maprs75932628
PheGenIrs75932628
Biobankrs75932628
1000 genomesrs75932628
hgdprs75932628
ensemblrs75932628
gopubmedrs75932628
geneviewrs75932628
scholarrs75932628
googlers75932628
pharmgkbrs75932628
gwascentralrs75932628
openSNPrs75932628
23andMers75932628
23andMe allrs75932628
SNP Nexus

SNPshotrs75932628
SNPdbers75932628
MSV3drs75932628
GWAS Ctlgrs75932628
GMAF0.002755
Max Magnitude3.5
rs75932628(T), a SNP in the TREM2 gene on chromosome 6 resulting in an R47H substitution, was found to confer a significantly higher risk of late-onset Alzheimer's disease based on two articles published together in 2013 in the New Engl. J. of Med.

In one study, the odds ratio for rs75932628(T) was 2.9 (CI: 2.09 to 4.09, P=3.42×10−10). The mutation had a frequency of 0.46% in controls 85 years of age or older. The authors also observed the association in additional sample sets (odds ratio, 2.90; 95% CI, 2.16 to 3.91; P=2.1×10−12 in combined discovery and replication samples), and found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer's disease had poorer cognitive function than noncarriers (P=0.003).[PMID 23150908OA-icon.png]

In the other study, analysis of the rs75932628(T) in a series that included 1887 patients with Alzheimer's disease showed a strong, highly significant association (odds ratio, 5.05, CI: 2.77 to 9.16; P=9.0×10−9). Four other TREM2 gene variants (D87N, T66M, Y38C, and Q33X) were also associated with higher risk for a frontotemporal dementia–like syndrome when homozygous.[PMID 23150934OA-icon.png]

A few subsequent studies, many - but not all - of which also see such an association, include:

[PMID 25936935OA-icon.png] Data shows that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (OR 2.71, p = 4.67 × 10e-25).

[PMID 25160042OA-icon.png] Based on a study of ~1,000 Alzheimer patients, the R47H mutation does appear to be a risk factor for AD (OR = 2.19, CI:1.04-4.51, p = .03). Individuals with p.R47H associated AD (n = 12) had significantly earlier symptom onset than individuals with no TREM2 variants (n = 551) (55.2 years vs. 61.7 years (p = .02).

[PMID 26058841OA-icon.png] Based on a Caucasian population comprising ~1,600 late-onset Alzheimer cases, carriers of the R47H variant are at increased risk (OR 7.40, p = 3.66e-06).

[PMID 25260849] A study of 474 AD patients from the northwest region of the UK showed a significant association of the R47H mutation with AD (OR 11.08, CI: 2.55-48.09, and Yates' corrected p value = 0.000146).

[PMID 25186855OA-icon.png] Meta-analysis of 2 family-based and 5 case-control cohorts yielded an overall summary estimate (using case-control data only) for an odds ratio of 1.67 (CI: 0.95-2.92) for the association between the TREM2 R47H and increased AD risk; so while this study replicates the association, it finds a weaker effect than have other studies.

[PMID 24041969] A study of ~3,000 AD patients from Spain did see the R47H association with AD (OR 4.12, CI: 1.21-14.00, p = 0.014). A meta-analysis comprising 32,598 subjects from 4 previous studies demonstrated the large effect of the p.R47H variant in AD risk (OR 4.11, CI: 2.99-5.68, p = 5.27×10e-18).

[PMID 24762945] No association was seen between R47H and AD in a study of ~2,000 Japanese patients with late-onset AD.

Additional studies include:


[PMID 23391427OA-icon.png] TREM2 is associated with the risk of Alzheimer's disease in Spanish population

[PMID 23800361OA-icon.png] TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson's disease

[PMID 24041969] Assessing the role of the TREM2 p.R47H variant as a risk factor for Alzheimer's disease and frontotemporal dementia

[PMID 24602511] Triggering receptor expressed on myeloid cells 2 variants are rare in Parkinson's disease in a Han Chinese cohort [PMID 23380991] TREM2 R47H variant as a risk factor for early-onset Alzheimer's disease.


[PMID 23510020OA-icon.png] Have we learnt all we need to know from genetic studies - is genetics over in Alzheimer's disease?


[PMID 23855982OA-icon.png] Assessment of TREM2 rs75932628 association with Alzheimer's disease in a population-based sample: the Cache County Study.

[PMID 25027412OA-icon.png] Frontobasal gray matter loss is associated with the TREM2 p.R47H variant

[PMID 25852195] Lack of Genetic Association Between TREM2 and Alzheimer's Disease in East Asian Population: A Systematic Review and Meta-Analysis

[PMID 26021840] Association Study of the TREM2 Gene and Identification of a Novel Variant in Exon 2 in Iranian Patients with Late-Onset Alzheimer's Disease

[PMID 26026943] Assessment of TREM2 rs75932628 association with amyotrophic lateral sclerosis in a Chinese population

[PMID 26058955] Assessment of TREM2 rs75932628 association with Parkinson's disease and multiple system atrophy in a Chinese population

[PMID 26058841OA-icon.png] More evidence for association of a rare TREM2 mutation (R47H) with Alzheimer's disease risk

ClinVar
Risk rs75932628(A;A) Rs75932628(T;T)
Alt rs75932628(A;A) Rs75932628(T;T)
Reference Rs75932628(C;C)
Significance Probable-non-pathogenic
Disease not specified
Variation info
Gene TREM2
CLNDBN not specified
Reversed 0
HGVS NC_000006.11:g.41129252C>T
CLNSRC
CLNACC RCV000175913.2,