ArticleAlzheimer's research & therapy2022
Mendelian randomization highlights significant difference and genetic heterogeneity in clinically diagnosed Alzheimer's disease GWAS and self-report proxy phenotype GWAX.
Article in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis 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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementias.Nature genetics · 2026Pooled it
- Downward bias in the association between APOE and Alzheimer's disease using prevalent and by-proxy disease sampling in the All of Us research program.BMC medical genomics · 2026Article
- Effects of ethanol leaf extract ofFrontiers in cellular neuroscience · 2026Article
- Distinguishing specific from broad genetic associations between external correlates and common factors.Bioinformatics (Oxford, England) · 2025Article
- Consensus meta-analysis of genome-wide association studies for Alzheimer's disease and related dementia.medRxiv : the preprint server for health sciences · 2025Article
- Volatile Organic Compounds (VOCs) in Neurodegenerative Diseases (NDDs): Diagnostic Potential and Analytical Approaches.Molecules (Basel, Switzerland) · 2025Review
- Robust Increase in IQCK Protein Expression in Mouse Models of Alzheimer's Disease and iPSC-Derived Neurons.Journal of cellular and molecular medicine · 2025Article
- Distinguishing Specific from Broad Genetic Associations between External Correlates and Common Factors.bioRxiv : the preprint server for biology · 2025Article
- Evaluating metabolome-wide causal effects on risk for psychiatric and neurodegenerative disorders.BMC medicine · 2025Article
- Transplantation of human glial cells into murine brains: A systematic review of efficacy and safety in neurodegenerative disorders.Current journal of neurology · 2025Review
- Role of miRNAs in the pathogenesis of psoriasis and psoriatic arthritis: a genome-wide Mendelian randomization study.Clinical rheumatology · 2025Article
- Molecular mechanisms and biomarkers in neurodegenerative disorders: a comprehensive review.Molecular biology reports · 2025Review
- Viruses and neurodegeneration: a growing concern.Journal of translational medicine · 2025Review
- Dynamic glycosylation remodeling in neurological disorders.Frontiers in molecular neuroscience · 2025Review
- Nerolidol-potential Therapeutic Agent for Various Neurological DisordersCurrent pharmaceutical biotechnology · 2025Review
- Examining the genetic relationship between Alzheimer's disease, schizophrenia and their shared risk factors using genomic structural equation modelling.Brain communications · 2025Article
- Unraveling human transferrin-tryptamine interactions: a computational and biophysical approach to Alzheimer's disease therapeutics.Frontiers in pharmacology · 2025Article
- The mediating role of primary sclerosing cholangitis in the association between ulcerative colitis and hepatobiliary cancer investigated through Mendelian randomization.Scientific reports · 2024Article
- Pervasive biases in proxy genome-wide association studies based on parental history of Alzheimer's disease.Nature genetics · 2024Article
- Assessing the validity of a self-reported clinical diagnosis of schizophrenia.Schizophrenia (Heidelberg, Germany) · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundUntil now, Mendelian randomization (MR) studies have investigated the causal association of risk factors with Alzheimer's disease (AD) using large-scale AD genome-wide association studies (GWAS), GWAS by proxy (GWAX), and meta-analyses of GWAS and GWAX (GWAS+GWAX) datasets. However, it currently remains unclear about the consistency of MR estimates across these GWAS, GWAX, and GWAS+GWAX datasets.
methodsHere, we first selected 162 independent educational attainment genetic variants as the potential instrumental variables (N = 405,072). We then selected one AD GWAS dataset (N = 63,926), two AD GWAX datasets (N = 314,278 and 408,942), and three GWAS+GWAX datasets (N = 388,324, 455,258, and 472,868). Finally, we conducted a MR analysis to evaluate the impact of educational attainment on AD risk across these datasets. Meanwhile, we tested the genetic heterogeneity of educational attainment genetic variants across these datasets.
resultsIn AD GWAS dataset, MR analysis showed that each SD increase in years of schooling (about 3.6 years) was significantly associated with 29% reduced AD risk (OR=0.71, 95% CI: 0.60-0.84, and P=1.02E-04). In AD GWAX dataset, MR analysis highlighted that each SD increase in years of schooling significantly increased 84% AD risk (OR=1.84, 95% CI: 1.59-2.13, and P=4.66E-16). Meanwhile, MR analysis suggested the ambiguous findings in AD GWAS+GWAX datasets. Heterogeneity test indicated evidence of genetic heterogeneity in AD GWAS and GWAX datasets.
conclusionsWe highlighted significant difference and genetic heterogeneity in clinically diagnosed AD GWAS and self-report proxy phenotype GWAX. Our MR findings are consistent with recent findings in AD genetic variants. Hence, the GWAX and GWAS+GWAX findings and MR findings from GWAX and GWAS+GWAX should be carefully interpreted and warrant further investigation using the AD GWAS dataset.
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.