ArticleProceedings of the National Academy of Sciences of the United States of America2021
Mendelian randomization identifies blood metabolites previously linked to midlife cognition as causal candidates in Alzheimer's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
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Who cites it
44 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- The causal association between circulating metabolites and Alzheimer's disease: a systematic review and meta-analysis of Mendelian randomization studies.Metabolomics : Official journal of the Metabolomic Society · 2025Pooled it
- Mendelian Randomization Analysis Reveals a Complex Genetic Interplay among Atopic Dermatitis, Asthma, and Gastroesophageal Reflux Disease.American journal of respiratory and critical care medicine · 2023Pooled it
- Dementia risk across distinct metabolic profiles in the UK Biobank.GeroScience · 2026Article
- Checking Genetic Homogeneity Between Two Samples Using Summary Statistics With Application to Mendelian Randomization.Statistics in medicine · 2026Article
- Analysis of whole genome sequencing and plasma metabolomics unveil genetic determinants and clinical implications for human health.Nature communications · 2026Article
- Unraveling Aberrant Metabolic Patterns in Alzheimer's Disease Subtypes: From Perturbed Metabolic Pathways to Candidate Drug Targets.Molecular neurobiology · 2026Article
- Systematic genetic investigation on relative macronutrient intake, circulating metabolic biomarkers and the risk of autoimmune diseases.NPJ science of food · 2025Article
- Integration of Metabolomic and Brain Imaging Data Highlights Pleiotropy Among Posttraumatic Stress Disorder, Glycoprotein Acetyls, and Pallidum Structure.Biological psychiatry global open science · 2025Article
- Evaluating metabolome-wide causal effects on risk for psychiatric and neurodegenerative disorders.BMC medicine · 2025Article
- Amyotrophic Lateral Sclerosis and Risk of Common Cancer: Mendelian Randomization Interrogation of Causality and Mediation.Phenomics (Cham, Switzerland) · 2025Article
- Assessing the potential causal effects of 1099 plasma metabolites on 2099 binary disease endpoints.Nature communications · 2025Article
- Genetic evidence for the liver-brain axis: lipid metabolism and neurodegenerative disease risk.Lipids in health and disease · 2025Article
- Lack of a Causal Association between DNA Methylation GrimAge Acceleration and Brain Tumor Incidence: A Two-Sample Mendelian Randomization Study.Journal of multidisciplinary healthcare · 2025Article
- A two-sample Mendelian randomization study on the relationship of body weight, body mass index, and waist circumference with cardiac arrest.World journal of emergency medicine · 2025Article
- Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study.Diabetes & metabolism journal · 2025Article
- Is the Relationship Between Cardiovascular Disease and Alzheimer's Disease Genetic? A Scoping Review.Genes · 2024Article
- Multi-omics insight into the metabolic and cellular characteristics in the pathogenesis of hypothyroidism.Communications biology · 2024Article
- Investigating Genetic Overlap between Alzheimer's Disease, Lipids, and Coronary Artery Disease: A Large-Scale Genome-Wide Cross Trait Analysis.International journal of molecular sciences · 2024Article
- Large-scale genome-wide association studies reveal the genetic causal etiology between air pollutants and autoimmune diseases.Journal of translational medicine · 2024Article
- Association between the circulating very long-chain saturated fatty acid and cognitive function in older adults: findings from the NHANES.BMC public health · 2024Article
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Authors and funding
9 authors.
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Abstract
There are currently no disease-modifying treatments for Alzheimer's disease (AD), and an understanding of preclinical causal biomarkers to help target disease pathogenesis in the earliest phases remains elusive. Here, we investigated whether 19 metabolites previously associated with midlife cognition-a preclinical predictor of AD-translate to later clinical risk, using Mendelian randomization (MR) to tease out AD-specific causal relationships. Summary statistics from the largest genome-wide association studies (GWASs) for AD and metabolites were used to perform bidirectional univariable MR. Bayesian model averaging (BMA) was additionally performed to address high correlation between metabolites and identify metabolite combinations that may be on the AD causal pathway. Univariable MR indicated four extra-large high-density lipoproteins (XL.HDL) on the causal pathway to AD: free cholesterol (XL.HDL.FC: 95% CI = 0.78 to 0.94), total lipids (XL.HDL.L: 95% CI = 0.80 to 0.97), phospholipids (XL.HDL.PL: 95% CI = 0.81 to 0.97), and concentration of XL.HDL particles (95% CI = 0.79 to 0.96), significant at an adjusted
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