|
rs104894002
|
|
|
0.020 |
GeneticVariation |
BEFREE |
Three variants in TREM2 (rs75932628 (R47H), rs2234255 (H157Y), and rs143332484 (R62H)) were significantly associated with AD risk, but the similar associations between rs104894002 (Q33X), rs2234253 (T96K), rs142232675 (D87N), rs2234256 (L211P), and AD were not proven.
|
30883352 |
2019 |
|
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 |
|
rs121908402
|
|
|
0.010 |
GeneticVariation |
BEFREE |
We identified 4 previously reported nonsynonymous variants (p.Asp39Glu, p.Arg62His, p.Thr96Lys, and p.Val126Gly) and 1 novel synonymous variant (p.Gln109Gln), none of which was significantly associated with the risk of Alzheimer's disease.
|
29723869 |
2018 |
|
rs142232675
|
|
|
0.010 |
GeneticVariation |
BEFREE |
Three variants in TREM2 (rs75932628 (R47H), rs2234255 (H157Y), and rs143332484 (R62H)) were significantly associated with AD risk, but the similar associations between rs104894002 (Q33X), rs2234253 (T96K), rs142232675 (D87N), rs2234256 (L211P), and AD were not proven.
|
30883352 |
2019 |
|
rs143332484
|
|
|
0.740 |
GeneticVariation |
BEFREE |
Three variants in TREM2 (rs75932628 (R47H), rs2234255 (H157Y), and rs143332484 (R62H)) were significantly associated with AD risk, but the similar associations between rs104894002 (Q33X), rs2234253 (T96K), rs142232675 (D87N), rs2234256 (L211P), and AD were not proven.
|
30883352 |
2019 |
|
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 |
|
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 |
|
rs143332484
|
|
|
0.740 |
GeneticVariation |
BEFREE |
Three variants in TREM2 (rs75932628 (R47H), rs2234255 (H157Y), and rs143332484 (R62H)) were significantly associated with AD risk, but the similar associations between rs104894002 (Q33X), rs2234253 (T96K), rs142232675 (D87N), rs2234256 (L211P), and AD were not proven.
|
30883352 |
2019 |
|
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 |
|
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 |
|
rs150277350
|
|
|
0.010 |
GeneticVariation |
BEFREE |
Together these data provide evidence that the A192T variant in TREM2 could contribute risk for AD.
|
28376694 |
2017 |
|
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 |
|
rs2234253
|
|
|
0.020 |
GeneticVariation |
BEFREE |
Three variants in TREM2 (rs75932628 (R47H), rs2234255 (H157Y), and rs143332484 (R62H)) were significantly associated with AD risk, but the similar associations between rs104894002 (Q33X), rs2234253 (T96K), rs142232675 (D87N), rs2234256 (L211P), and AD were not proven.
|
30883352 |
2019 |
|
rs2234253
|
|
|
0.020 |
GeneticVariation |
BEFREE |
We identified 4 previously reported nonsynonymous variants (p.Asp39Glu, p.Arg62His, p.Thr96Lys, and p.Val126Gly) and 1 novel synonymous variant (p.Gln109Gln), none of which was significantly associated with the risk of Alzheimer's disease.
|
29723869 |
2018 |
|
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 |
Three variants in TREM2 (rs75932628 (R47H), rs2234255 (H157Y), and rs143332484 (R62H)) were significantly associated with AD risk, but the similar associations between rs104894002 (Q33X), rs2234253 (T96K), rs142232675 (D87N), rs2234256 (L211P), and AD were not proven.
|
30883352 |
2019 |
|
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 |
|
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 |
|
rs2234256
|
|
|
0.010 |
GeneticVariation |
BEFREE |
Three variants in TREM2 (rs75932628 (R47H), rs2234255 (H157Y), and rs143332484 (R62H)) were significantly associated with AD risk, but the similar associations between rs104894002 (Q33X), rs2234253 (T96K), rs142232675 (D87N), rs2234256 (L211P), and AD were not proven.
|
30883352 |
2019 |
|
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 |
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 |
Lymphoblast-derived integration-free iPSC line AD-TREM2-3 from a 74 year-old Alzheimer's disease patient expressing the TREM2 p.R47H variant.
|
29902745 |
2018 |
|
rs75932628
|
|
|
0.900 |
GeneticVariation |
BEFREE |
Molecular basis for the loss-of-function effects of the Alzheimer's disease-associated R47H variant of the immune receptor TREM2.
|
29794134 |
2018 |
|
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 |