|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
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, 95% CI = 2.99-5.68, p = 5.27×10(-18)).
|
24041969 |
2014 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
A rare TREM2 missense mutation (rs75932628-T) was reported to confer a significant Alzheimer's disease (AD) risk.
|
26365049 |
2016 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Although R47H mutation in AD affected the glycosylation and normal trafficking of TREM2 less, the detailed pattern of glycosylated TREM2 differs from that of the wild type, thus suggesting that precise regulation of TREM2 glycosylation is impaired when arginine at 47 is mutated to histidine.
|
25615530 |
2015 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Although rs75932628 in triggering receptor expressed on myeloid cells 2 (TREM2) was shown to increase the risk for Alzheimer's disease, there is no agreement on the association between this variant and the risk for Parkinson's disease (PD).
|
26058955 |
2015 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Although, rs75932628 in triggering receptor expressed on myeloid cells 2 (TREM2) was shown to increase the risk for Alzheimer's disease, there is no agreement on the association between this variant and the risk for amyotrophic lateral sclerosis (ALS).
|
26026943 |
2015 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
ApoE4, TREM2 R47H, and rare variants in other genes, such as UNC5C D353N, are likely responsible for the notable occurrence of AD in this family.
|
26076170 |
2015 |
|
rs201280312
|
|
|
0.010 |
GeneticVariation |
BEFREE |
As a result, none of these 3 variants were identified in all subjects, however, 1 novel variant (p.A130V) in TREM2 and 4 novel variants (p.Q860H, p.T837K, p.S843G, and p.V836V) in UNC5C were detected in unrelated patients with late-onset AD.
|
24866402 |
2014 |
|
rs2234255
|
|
|
0.050 |
GeneticVariation |
BEFREE |
Crucially, we also show that the Alzheimer's disease-associated H157Y TREM2 variant was shed more rapidly than wild type from HEK293 cells, possibly by a novel, batimastat- and ADAM10-siRNA-independent, sheddase activity.
|
28855301 |
2017 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Expression and processing analyses of wild type and p.R47H TREM2 variant in Alzheimer's disease brains.
|
27887626 |
2016 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Aβ42 suggesting that TREM2's role in AD may involve tau dysfunction.
|
25936935 |
2015 |
|
rs753325601
|
|
|
0.010 |
GeneticVariation |
BEFREE |
Given recent findings of enrichment of rare TREM2 variants (including R47C) in Alzheimer's disease, it is notable that we detected a homozygous TREM2 R47C carrier presenting with an FTD rather than an Alzheimer's disease phenotype.
|
29748150 |
2018 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease through impaired containment of inflammatory processes.
|
23150908 |
2013 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Here, we report the first positive replication study in a Spanish population and confirm that TREM2 rs75932628-T is associated with the risk for AD.
|
23391427 |
2013 |
|
rs143332484
|
|
|
0.740 |
GeneticVariation |
BEFREE |
However, the isoform which lacks the 5' exon, but includes the transmembrane domain, was significantly lower in TREM2- p.R62H carriers than in AD cases (p = 0.007).
|
31068200 |
2019 |
|
rs766647311
|
|
|
0.010 |
GeneticVariation |
BEFREE |
In a whole-exome sequencing study of a family with probable AD-type dementia without pathogenic variants in known autosomal dominant dementia disease genes and negative for the apolipoprotein E (APOE) ε4 allele, we identified an extremely rare TREM2 coding variant, that is, a glycine-to-tryptophan substitution at amino acid position 145 (NM_018965.3:c.433G>T/p.[Gly145Trp]).
|
31464095 |
2020 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
In addition to Alzheimer's disease risk, we also examined the association of R47H with Alzheimer's disease-related phenotypes, including age-at-onset, psychosis, and amyloid deposition but found no significant association.
|
26058841 |
2015 |
|
rs149622783
|
|
|
0.010 |
GeneticVariation |
BEFREE |
In addition, we identified rare variant R136Q in a patient with language-predominant AD that also showed impaired surface expression.
|
27589997 |
2016 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
In contrast, CSF sTREM2 levels were significantly higher in R47H carriers compared to non-carriers (P = 6×10(-3)), suggesting that this variant does not impact protein expression and increases AD risk through a different pathogenic mechanism than NHD variants.
|
26754641 |
2016 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
In overall meta-analysis, the summary ORs for rs75932628, rs104894002, and rs143332484 were 2.70 [95% CI: 2.24, 3.24; P < 0.001], 7.21 (95% CI: 1.28, 40.78; P = 0.025), and 1.65 (95% CI: 1.24, 2.21; P = 0.001), respectively, indicating that the TREM2 rs75932628, rs104894002, and rs143332484 may contribute to AD risk.
|
26037549 |
2015 |
|
rs104894002
|
|
|
0.020 |
GeneticVariation |
BEFREE |
In overall meta-analysis, the summary ORs for rs75932628, rs104894002, and rs143332484 were 2.70 [95% CI: 2.24, 3.24; P < 0.001], 7.21 (95% CI: 1.28, 40.78; P = 0.025), and 1.65 (95% CI: 1.24, 2.21; P = 0.001), respectively, indicating that the TREM2 rs75932628, rs104894002, and rs143332484 may contribute to AD risk.
|
26037549 |
2015 |
|
rs143332484
|
|
|
0.740 |
GeneticVariation |
BEFREE |
In overall meta-analysis, the summary ORs for rs75932628, rs104894002, and rs143332484 were 2.70 [95% CI: 2.24, 3.24; P < 0.001], 7.21 (95% CI: 1.28, 40.78; P = 0.025), and 1.65 (95% CI: 1.24, 2.21; P = 0.001), respectively, indicating that the TREM2 rs75932628, rs104894002, and rs143332484 may contribute to AD risk.
|
26037549 |
2015 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Independent voxel-based morphometry analysis of the Spanish set as well as conjunction and joint analyses revealed substantial gray matter loss in orbitofrontal cortex and anterior cingulate cortex with relative preservation of parietal lobes in AD and/or mild cognitive impairment TREM2 p.R47H carriers, suggesting that TREM2 p.R47H variant is associated with certain clinical and neuroimaging AD features in addition to the increased TREM2 p.R47H atrophy in temporal lobes as described previously.
|
25027412 |
2014 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Lymphoblast-derived integration-free iPS cell line from a 65-year-old Alzheimer's disease patient expressing the TREM2 p.R47H variant.
|
27345793 |
2016 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Lymphoblast-derived integration-free iPS cell line from a female 67-year-old Alzheimer's disease patient with TREM2 (R47H) missense mutation.
|
27789408 |
2016 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Lymphoblast-derived integration-free iPSC line AD-TREM2-1 from a 67year-old Alzheimer's disease patient expressing the TREM2 p.R47H variant.
|
29602048 |
2018 |