ArticleGenome medicine2023
Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.
Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Contributions of the Alzheimer's Disease Neuroimaging Initiative to advancing AD research: a targeted review of recent publications.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Genetic analysis of neurodegenerative diseases.The Journal of clinical investigation · 2026Review
- Exploratory RNA Sequencing Reveals Systemic Metabolic Dysregulation in Alzheimer's Disease: Insights from a Diverse Latin American Cohort.Molecular neurobiology · 2026Article
- An integrative neurogenomics workflow for precision medicine in neurodegenerative disorders.Frontiers in dementia · 2026Article
- Article
- Modeling Alzheimer's disease: Bayesian copula graphical model from demographic, cognitive, and neuroimaging data.Journal of Alzheimer's disease : JAD · 2025Article
- Gut microbiota mediates semaglutide attenuation of diabetes-associated cognitive decline.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Uncovering leading compounds for alzheimer's disease treatment: mendelian randomization and virtual screening insights into plasma protein modulation.Biological research · 2025Article
- Alzheimer's disease and other memory disorders in the age of AI: reflection and perspectives on the 120th anniversary of the birth of Dr. John von Neumann.GeroScience · 2025Review
- Lessons from national biobank projects utilizing whole-genome sequencing for population-scale genomics.Genomics & informatics · 2025Review
- Assessment of genetic associations between antidepressant drug targets and various stroke subtypes: A Mendelian randomization approach.Chinese medical journal · 2025Article
- Exome sequencing reveals a rare damaging variant in GRIN2C in familial late-onset Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Multi-Omics Integration Analysis Pinpoint Proteins Influencing Brain Structure and Function: Toward Drug Targets and Neuroimaging Biomarkers for Neuropsychiatric Disorders.International journal of molecular sciences · 2024Article
- Unveiling the Therapeutic Potential of Kelulut (Stingless Bee) Honey in Alzheimer's Disease: Findings from a Rat Model Study.Antioxidants (Basel, Switzerland) · 2024Article
- Review
- Top 100 most-cited articles on tau protein: a bibliometric analysis and evidence mapping.Frontiers in neuroscience · 2024Article
- Multivariate GWAS of Alzheimer's disease CSF biomarker profiles implies GRIN2D in synaptic functioning.Genome medicine · 2023Article
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Authors and funding
42 authors at 20 institutions in 11 countries.
Funding
Abstract
backgroundGenome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.
methodsWe performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n = 205 controls, n = 546 mild cognitive impairment, n = 222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects.
resultsFive loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers.
conclusionsThese results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.
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