ArticleJournal of Alzheimer's disease : JAD2020
Whole-Exome Sequencing Analysis of Alzheimer's Disease in Non-APOE*4 Carriers.
Article in Journal of Alzheimer's disease : JAD, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 3 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Pooled it
- Investigation of the independent role of a rare APOE variant (L28P; APOE*4Pittsburgh) in late-onset Alzheimer disease.Neurobiology of aging · 2023Pooled it
- Guidelines for bioinformatics of single-cell sequencing data analysis in Alzheimer's disease: review, recommendation, implementation and application.Molecular neurodegeneration · 2022Pooled it
- Genetic background and multidomain interventions in mild cognitive impairment.Alzheimer's research & therapy · 2025Trial
- Golgi dysfunction in Alzheimer disease: from human multiomic signatures to therapeutic targets.Experimental & molecular medicine · 2026Review
- PreoperativeFrontiers in bioinformatics · 2026Review
- Genome-wide association of tau neuroimaging and plasma biomarkers in adults with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Integrative single-cell RNA sequencing and mendelian randomization analysis reveal the potential role of synaptic vesicle cycling-related genes in Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Article
- Genetic overlap between cortical brain morphometry and frontotemporal dementia risk.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Rare variant aggregation in 148,508 exomes identifies genes associated with proxy dementia.Scientific reports · 2023Article
- Microglia in Alzheimer's disease: pathogenesis, mechanisms, and therapeutic potentials.Frontiers in aging neuroscience · 2023Review
- Novel Genetic Variants in TP37, PIK3R1, CALM1, and PLCG2 of the Neurotrophin Signaling Pathway Are Associated with the Progression from Mild Cognitive Impairment to Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Article
- Genomics and Functional Genomics of Alzheimer's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Genomics of Alzheimer's disease implicates the innate and adaptive immune systems.Cellular and molecular life sciences : CMLS · 2021Review
- Searching the Dark Genome for Alzheimer's Disease Risk Variants.Brain sciences · 2021Review
- Reassessment of Pioglitazone for Alzheimer's Disease.Frontiers in neuroscience · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The genetics of late-onset Alzheimer's disease (AD) is complex due to the heterogeneous nature of the disorder. APOE*4 is the strongest genetic risk factor for AD. Genome-wide association studies have identified more than 30 additional loci, each having relatively small effect size. Known AD loci explain only about 30% of the genetic variance, and thus much of the genetic variance remains unexplained. To identify some of the missing heritability of AD, we analyzed whole-exome sequencing (WES) data focusing on non-APOE*4 carriers from two WES datasets: 720 cases and controls from the University of Pittsburgh and 7,252 cases and controls from the Alzheimer's Disease Sequencing Project. Following separate WES analyses in each dataset, we performed meta-analysis for overlapping markers present in both datasets. Among the four variants reaching the exome-wide significance threshold, three were from known AD loci: APOE/rs7412 (odds ratio (OR) = 0.40; p = 5.46E-24), TOMM40/rs157581 (OR = 1.49; p = 4.04E-07), and TREM2/rs75932628 (OR = 4.00; p = 1.15E-07). The fourth significant variant, rs199533, was from a novel locus on chromosome 17 in the NSF gene (OR = 0.78; p = 2.88E-07). NSF was also significant in the gene-based analysis (p = 1.20E-05). In the GTEx data, NSF/rs199533 is a cis-eQTL for multiple genes in the brain and blood, including NSF that is highly expressed across all brain tissues, including regions that typically show amyloid-β accumulation. Further characterization of genes that are affected by NSF/rs199533 may help to shed light on the roles of these genes in AD etiology.
Indexed as
Identifiers
What OpenQuestion holds
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.