ArticleGenetic epidemiology2019
Integrated analysis of genomics, longitudinal metabolomics, and Alzheimer's risk factors among 1,111 cohort participants.
Article in Genetic epidemiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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
40 citing papers in PubMed, 55 citations in OpenAlex.
- Trial
- Impact of IL-6 receptor inhibitors on cerebrospinal fluid metabolites in type 2 diabetes patients.Medicine · 2026Article
- Untargeted and Targeted Cerebrospinal Fluid Neurometabolomics via Chromatography-Mass Spectrometry-Based Methods.Molecules (Basel, Switzerland) · 2026Review
- Cerebrospinal fluid metabolites and their association with female reproductive disorders: insights from mendelian randomization.Journal of ovarian research · 2026Article
- Cognitive-behavioral phenotypes inFrontiers in molecular neuroscience · 2026Article
- APOE, ABCA7, and RASGEF1C are associated with earlier onset of amyloid deposition from more than 4000 harmonized positron emission tomography images.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Integrative analysis of cerebrospinal fluid biomarkers, metabolomics, and polygenic risk reveals novel metabolite associations with Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Article
- A new role for PHYHD1 and related dioxygenases: demethylation of 2'-O-methylated nucleosides.Nucleic acids research · 2025Article
- Exploring the Causal Links Between 338 Cerebrospinal Fluid Metabolites and Parkinson's Disease.Brain and behavior · 2025Article
- Nuclear Magnetic Resonance Analysis Implicates Sex-Specific Dysregulation of the Blood Lipids in Alzheimer's Disease: A Retrospective Health-Controlled Study.Psychiatry investigation · 2024Article
- Mid-to-Late Life Healthy Lifestyle Modifies Genetic Risk for Longitudinal Cognitive Aging among Asymptomatic Individuals.medRxiv : the preprint server for health sciences · 2024Article
- Apolipoprotein E moderates the association between non-APOE polygenic risk score for Alzheimer's disease and aging on preclinical cognitive function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Inferring Alzheimer's disease pathologic traits from clinical measures in living adults.medRxiv : the preprint server for health sciences · 2024Article
- Inferring Alzheimer's Disease Pathologic Traits from Clinical Measures in Living Adults.Journal of Alzheimer's disease : JAD · 2024Article
- Monitoring central nervous system tumour metabolism using cerebrospinal fluid.Frontiers in oncology · 2024Review
- Large-scale proteome and metabolome analysis of CSF implicates altered glucose and carbon metabolism and succinylcarnitine in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Assessing the Biological Mechanisms Linking Smoking Behavior and Cognitive Function: A Mediation Analysis of Untargeted Metabolomics.Metabolites · 2023Article
- Metabolomic epidemiology offers insights into disease aetiology.Nature metabolism · 2023Review
- Cognitive trajectories diverge by genetic risk in a preclinical longitudinal cohort.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Apolipoprotein E moderates the association between Non-medRxiv : the preprint server for health sciences · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
Abstract
Although Alzheimer's disease (AD) is highly heritable, genetic variants are known to be associated with AD only explain a small proportion of its heritability. Genetic factors may only convey disease risk in individuals with certain environmental exposures, suggesting that a multiomics approach could reveal underlying mechanisms contributing to complex traits, such as AD. We developed an integrated network to investigate relationships between metabolomics, genomics, and AD risk factors using Wisconsin Registry for Alzheimer's Prevention participants. Analyses included 1,111 non-Hispanic Caucasian participants with whole blood expression for 11,376 genes (imputed from dense genome-wide genotyping), 1,097 fasting plasma metabolites, and 17 AD risk factors. A subset of 155 individuals also had 364 fastings cerebral spinal fluid (CSF) metabolites. After adjusting each of these 12,854 variables for potential confounders, we developed an undirected graphical network, representing all significant pairwise correlations upon adjusting for multiple testing. There were many instances of genes being indirectly linked to AD risk factors through metabolites, suggesting that genes may influence AD risk through particular metabolites. Follow-up analyses suggested that glycine mediates the relationship between carbamoyl-phosphate synthase 1 and measures of cardiovascular and diabetes risk, including body mass index, waist-hip ratio, inflammation, and insulin resistance. Further, 38 CSF metabolites explained more than 60% of the variance of CSF levels of tau, a detrimental protein that accumulates in the brain of AD patients and is necessary for its diagnosis. These results further our understanding of underlying mechanisms contributing to AD risk while demonstrating the utility of generating and integrating multiple omics data types.
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.