|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We show that long-read sequencing with a single Oxford Nanopore Technologies PromethION flow cell per individual achieves 30× human genome coverage and enables accurate assessment of tandem repeats including the 10,000-bp Alzheimer's disease-associated ABCA7 VNTR.
|
31727106 |
2019 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Collectively, our analysis further supports previous findings that the ABCA7 rs3764650 polymorphism is associated with AD susceptibility.
|
24643655 |
2014 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Massive parallel sequencing recently allowed the identification of three genes carrying a higher burden of rare, protein-truncating and missense predicted damaging variants in Alzheimer disease (AD) cases as compared to controls: TREM2, SORL1, and ABCA7.
|
30911827 |
2019 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
All patients carrying a loss-of-function mutation in ABCA7 exhibited a classical Alzheimer disease phenotype, though with a striking wide onset age range, suggesting the influence of unknown modifying factors.
|
27037232 |
2016 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
There were four significant associations between genotypes and phenotypes of AD patients: CR1 SNP rs11803956 correlated with Mini-Mental State Examination (MMSE) score (β=1.718, Pcorrected=0.002); ABCA7 SNP rs3752232 correlated with Rey Complex Figure Test (RCFT) copy score (β=-6.861, Pcorrected=0.013); APOE SNP rs2075650 correlated with the percentile of RCFT copy score (β=14.005, Pcorrected=0.021) and the percentile of total score in phonemic fluency (β=11.052, Pcorrected=0.035).
|
24530172 |
2014 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
In conclusion, ABCA7 genetic variants, especially the LOF mutations, were significantly associated with the risk of AD.
|
29782324 |
2018 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Several genes associated with AD risk-most notably, the ε4 allele of the apolipoprotein E (APOE) gene and several mutations in the ATP-binding cassette transporter A7 (ABCA7) gene-are linked to altered lipid metabolism, especially in AAs.
|
30747415 |
2019 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Thus, our study suggested that ABCA7 genotypes contribute to the AD risk through involvement in amyloid-β deposition on in vivo imaging, but not in tau pathology, brain atrophy, or decreased glucose metabolism.
|
27003212 |
2016 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Besides the previously reported APOE and CR1 loci, we found that the ABCA7 (rs3764650; P = .02) and CD2AP (rs9349407; P = .03) AD susceptibility loci are associated with neuritic plaque burden.
|
23836404 |
2013 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
The effect of loss-of-function mutations on ABCA7 expression was investigated with quantitative real-time PCR in post-mortem brains of patients (n=3) and control individuals (n=4); nonsense mediated mRNA decay was investigated in lymphoblast cell lines from three predicted loss-of-function mutation carriers from the cohort of 772 patients with Alzheimer's disease.
|
26141617 |
2015 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
GWASCAT |
Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project.
|
31473137 |
2019 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
GWASCAT |
Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans.
|
23571587 |
2013 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Similarly, the more prevalent late-onset forms of AD are associated with both coding and non-coding variants in genes such as SORL1, PICALM and ABCA7 that affect the production and clearance of Aβ.
|
25748120 |
2015 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
To probe for a function of ABCA7 in vivo, we crossed Abca7(-/-) mice with J20 mice, an amyloidogenic transgenic AD mouse model [B6.Cg-Tg(PDGFB-APPSwInd)20Lms/J] expressing a mutant form of human APP bearing both the Swedish (K670N/M671L) and Indiana (V717F) familial AD mutations.
|
26517904 |
2015 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
GWASCAT |
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.
|
24162737 |
2013 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
ABCA7 rs3764650 was significantly associated with AD and the GG genotype carried a reduced risk for AD (odds ratio = 0.52, p = 0.0026).
|
24908168 |
2014 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Thus, in African Americans the interactive effects of ABCA7 rs3764650 and aerobic fitness likely compound overall ABCA7-related AD risk, and may contribute to health disparities whereby African Americans are at a higher risk for dementia, with double the prevalence of AD.
|
31024289 |
2019 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
None of the AD-susceptibility loci (ABCA7, APOE, CLU, CR1, and PICALM) showed statistically significant association with PD susceptibility.
|
23820587 |
2013 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
There are other cis-variants that significantly influence brain expression of CLU and ABCA7 (p = 4.01 × 10(-5)-9.09 × 10(-9)), some of which also associate with AD risk (p = 2.64 × 10(-2)-6.25 × 10(-5)).
|
22722634 |
2012 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
The pooled effect of ABCA7 rs3764605 allele G was significantly associated with an increased the risk of AD (OR=1.20, 95% CI: 1.14-1.26, P value <0.001).
|
26795201 |
2016 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
In conclusion, this meta-analysis suggested that ABCA7 rs3764650 polymorphism is significantly associated with AD risk.
|
29441941 |
2017 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
GWASDB |
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.
|
24162737 |
2013 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
In total, we identified 78 potentially damaging rare variants (frequency <1%), including ABCA7 p.L400V in a family with Alzheimer's disease and LRRK2 p.R1514Q in 6 of 98 patients with Parkinson's disease (6.1%).
|
25174650 |
2015 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
These results confirm that ABCA7 LOF variants are enriched in patients with AD and extend this finding to predicted damaging missense variants.
|
27037229 |
2016 |
|
Alzheimer's Disease
|
0.500 |
GeneticVariation
|
disease |
GWASCAT |
Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.
|
30617256 |
2019 |