|
rs143332484
|
|
|
0.740 |
GeneticVariation |
BEFREE |
We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10<sup>-10</sup>, odds ratio (OR) = 0.68, minor allele frequency (MAF)<sub>cases</sub> = 0.0059, MAF<sub>controls</sub> = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10<sup>-10</sup>, OR = 1.43, MAF<sub>cases</sub> = 0.011, MAF<sub>controls</sub> = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10<sup>-14</sup>, OR = 1.67, MAF<sub>cases</sub> = 0.0143, MAF<sub>controls</sub> = 0.0089), a known susceptibility gene for Alzheimer's disease.
|
28714976 |
2017 |
|
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 |
|
rs2234255
|
|
|
0.050 |
GeneticVariation |
BEFREE |
TREM2 is shed by proteases of the ADAM (a disintegrin and metalloproteinase domain containing protein) family C-terminal to histidine 157, a position where an AD-associated coding variant has been discovered (p.H157Y) in the Han Chinese population.
|
28855300 |
2017 |
|
rs150277350
|
|
|
0.010 |
GeneticVariation |
BEFREE |
Together these data provide evidence that the A192T variant in TREM2 could contribute risk for AD.
|
28376694 |
2017 |
|
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 |
Two rare variants have been nominally associated with AD risk or protection (TREM2 p.R47H, MAF approximately 0.002, OR approximately 4 and APP p.A673T, MAF approximately 0.0005, OR approximately 0.2).
|
28002825 |
2016 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
The previously reported functional mutation rs75932628-T (p.R47H) in the triggering receptor expressed on myeloid cells 2 (TREM2) is a genetic risk factor for Alzheimer's disease, Parkinson's disease (PD) and frontotemporal dementia, in European populations.
|
26758262 |
2016 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Our study suggests that Vps35/retromer is responsible for recycling of Trem2 in the regulation of microglial function such as proinflammatory responses, whereas R47H mutation impairs Trem2 trafficking, which might contribute to AD.
|
27717139 |
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 |
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 |
TREM2 encodes a cell surface receptor expressed on microglia and related cells, and the R47H variant associated with AD appears to affect the ability of TREM2 to bind extracellular ligands.
|
27589997 |
2016 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Two recent studies have identified that a rare coding variant (p.R47H) in exon 2 of triggering receptor expressed on myeloid cells 2 (TREM2) gene is associated with Alzheimer's disease (AD) susceptibility in Caucasians.
|
27067662 |
2016 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
The different biochemical characteristics of TREM2 R47H, including glycosylation, solubility and processing, may offer insights into a future therapeutic strategy for AD.
|
28149270 |
2016 |
|
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 |
Recent genome-wide association studies revealed TREM2 rs75932628-T variant to be associated with Alzheimer's disease (AD) and other neurodegenerative diseases.
|
27051467 |
2016 |
|
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 |
|
rs2234255
|
|
|
0.050 |
GeneticVariation |
BEFREE |
To gain a credible conclusion on the association between p.H157Y and AD risk, a meta-analysis involving 7,102 cases and 7,408 controls was conducted.
|
27501831 |
2016 |
|
rs2234255
|
|
|
0.050 |
GeneticVariation |
BEFREE |
We provided the first evidence that a rare coding variant (p.H157Y) in TREM2 exon 3 conferred a considerable risk of AD in our cohort (Pcorrected = 0.02, odds ratio = 11.01, 95% confidence interval: 1.38-88.05).
|
27067662 |
2016 |
|
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 |
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 |
The results showed that rs75932628 variant was significantly associated with AD in caucasian population (P < .001, odds ratio ¼ 3.17, 95% confidence interval 2.45-4.09).
|
25852195 |
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 |
Several studies have shown that TREM2 gene variant rs75932628-T increased the risks for Alzheimer's disease (AD), Parkinson's disease, frontotemporal dementia and amyotrophic lateral sclerosis.
|
25186950 |
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 |
|
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 |