ArticleAlzheimer's research & therapy2018
Genome-wide association study for variants that modulate relationships between cerebrospinal fluid amyloid-beta 42, tau, and p-tau levels.
Article in Alzheimer's research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Pooled it
- Quantitative trait loci, G×E and G×G for glycemic traits: response to metformin and placebo in the Diabetes Prevention Program (DPP).Journal of human genetics · 2022Trial
- The role of GZMA as a target of cysteine and biomarker in Alzheimer's disease, pelvic organ prolapse, and tumor progression.Frontiers in pharmacology · 2024Article
- Magnetic transferrin nanoparticles (MTNs) assay as a novel isolation approach for exosomal biomarkers in neurological diseases.Biomaterials research · 2023Article
- The genetic regulation of protein expression in cerebrospinal fluid.EMBO molecular medicine · 2023Article
- Clinical effects of novel susceptibility genes for beta-amyloid: a gene-based association study in the Korean population.Frontiers in aging neuroscience · 2023Article
- Article
- Systematic Search for Novel Circulating Biomarkers Associated with Extracellular Vesicles in Alzheimer's Disease: Combining Literature Screening and Database Mining Approaches.Journal of personalized medicine · 2021Article
- Admixture mapping reveals the association between Native American ancestry at 3q13.11 and reduced risk of Alzheimer's disease in Caribbean Hispanics.Alzheimer's research & therapy · 2021Article
- RAB10: an Alzheimer's disease resilience locus and potential drug target.Clinical interventions in aging · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundA relationship quantitative trait locus exists when the correlation between multiple traits varies by genotype for that locus. Relationship quantitative trait loci (rQTL) are often involved in gene-by-gene (G×G) interactions or gene-by-environmental interactions, making them a powerful tool for detecting G×G.
methodsWe performed genome-wide association studies to identify rQTL between tau and Aβ42 and ptau and Aβ42 with over 3000 individuals using age, gender, series, APOE ε2, APOE ε4, and two principal components for population structure as covariates. Each significant rQTL was separately screened for interactions with other loci for each trait in the rQTL model. Parametric bootstrapping was used to assess significance.
resultsWe found four significant tau/Aβ42 rQTL from three unique locations and six ptau/Aβ42 rQTL from five unique locations. G×G screens with these rQTL produced four significant G×G interactions (one Aβ42, two ptau, and one tau) with four rQTL where each second locus was from a unique location. On follow-up, rs1036819 and rs74025622 were associated with Alzheimer's disease (AD) case/control status; rs15205 and rs79099429 were associated with rate of decline.
conclusionsThe two most significant rQTL (rs8027714 and rs1036819) for ptau/Aβ42 are on different chromosomes and both are strong hits for pelvic organ prolapse. While diseases of the nervous system can cause pelvic organ prolapse, it is unlikely related to the ptau/Aβ42 relationship but may suggest that these two loci share a pathway. In addition to a ptau/Aβ42 rQTL and association with AD case/control status, rs1036819 is a strong rQTL for case/control status/Aβ42 and for tau/Aβ42. It resides in the ZFAT gene, which is related to autoimmune thyroid disease. For tau, rs9817620 interacts with the tau/Aβ42 rQTL rs74025622. It is in the CHL1 gene, which is a neural cell adhesion molecule and may be involved in signal transduction pathways. CHL1 is related to BACE1, which is a β-secretase enzyme that initiates production of the β-amyloid peptide involved in AD and is a primary drug target. Overall, there are numerous loci that affect the relationship between these important AD endophenotypes and some are due to interactions with other loci. Some affect the risk of AD and/or rate of progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.