ArticleNature genetics2024
Genetic architecture of cerebrospinal fluid and brain metabolite levels and the genetic colocalization of metabolites with human traits.
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Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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28citing papers in PubMed, 1 pooled it
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- GWAS meta-analysis of cerebrospinal fluid Alzheimer's biomarkers reveals loci regulating lipids, brain volume and autophagy.Nature communications · 2026Pooled it
- NTPDase2 suppresses hippocampal astrocyte-supplied cholesterol through hydrolyzing eATP in depression.Molecular psychiatry · 2026Article
- Exploratory bidirectional Mendelian randomisation analysis of cerebrospinal fluid metabolites associated with cerebral palsy and epilepsy.BMJ paediatrics open · 2026Article
- Mapping the causal chain from genetic risk variants to lipid dysmetabolism in Parkinson's disease.Brain : a journal of neurology · 2026Article
- Integrated proteomic, transcriptomic, and epigenomic profiling identifies SRA1 as a novel therapeutic target for postpartum depression.Npj mental health research · 2026Article
- Polyamide-66 microplastics and early-onset ischemic stroke: a systems toxicology, multi-omics, and molecular dynamics simulation analysis.Molecular diversity · 2026Article
- Reduced LACTB expression in myeloid cells is associated with elevated succinylcarnitine and reduced Alzheimer's disease risk.Research square · 2026Article
- Polyol pathway dysregulation in CSF links glucose metabolism to tau pathology independently of amyloid and genetic predisposition.medRxiv : the preprint server for health sciences · 2026Article
- APOE-stratified Proteomic and Metabolomic Analysis Reveals Mitochondrial Dysfunction Inflammation and Lipid Dysregulation in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cerebrospinal fluid and plasma metabolites in Parkinson's disease: a Mendelian randomization study.Scientific reports · 2026Article
- Understanding Neurodegenerative Diseases From the -Omics Perspective: Lessons Learnt.Annals of neurology · 2026Review
- Article
- Ethnic-specific effects of the LILRB2-LILRB5 locus and newly identified risk loci for Alzheimer's disease in the East Asian population.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Analyses of plasma multi-omic data across ancestries identify novel pathways implicated in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Imaging-mediated genetic effects link brain microstructure, metabolic profiles, and regional transcription to glioma susceptibility.Frontiers in immunology · 2026Article
- A multi-omics framework integrating gut microbiota, blood metabolites, and immune cells to elucidate the pathogenesis of Alzheimer's disease.Frontiers in immunology · 2026Article
- Article
- Dissecting the Causal Pathway from Herpes Zoster to Postherpetic Neuralgia: A Multi-Stage Mendelian Randomization Study Implicating VZV-Specific IgE and Cerebrospinal Fluid Metabolites.Journal of pain research · 2026Article
- 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
- Genetic regulation of the metabolome differs by sex, Alzheimer's disease stage, and plasma biomarker status.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
Corrections and comments
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Authors and funding
28 authors.
Ciyang WangDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-5253-0490
Chengran YangDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-4577-5590
Daniel WesternDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-3725-9553
Muhammad AliDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-1399-6631
Yueyao WangDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0003-3288-1180
Chia-Ling PhuahNeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA.
John BuddeDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-7778-7276
Lihua WangDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Priyanka GorijalaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Jigyasha TimsinaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Agustin RuizResearch Center and Memory Clinic, ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0003-2633-2495
Pau PastorUnit of Neurodegenerative Diseases, Department of Neurology, University Hospital Germans Trias i Pujol, Badalona, Spain.ORCID http://orcid.org/0000-0002-7493-8777
Maria Victoria FernandezDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-9669-5147
Dominantly Inherited Alzheimer Network (DIAN)
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Daniel J PanyardDepartment of Genetics, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-5480-4803
Corinne D EngelmanDepartment of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Yuetiva DemingWisconsin Alzheimer's Disease Research Center, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0001-7512-5703
Merce BoadaResearch Center and Memory Clinic, ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0003-2617-3009
Amanda CanoResearch Center and Memory Clinic, ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.
Pablo Garcia-GonzalezResearch Center and Memory Clinic, ACE Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, Spain.ORCID http://orcid.org/0000-0003-0125-5403
Neill R Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, FL, USA.
Hiroshi MoriDepartment of Clinical Neuroscience, Faculty of Medicine, Osaka Metropolitan University, Osaka, Japan.
Jae-Hong LeeUniversity of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Richard J PerrinHope Center for Neurologic Disorders, Washington University, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-3443-7716
Laura IbanezDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Yun Ju SungDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-8021-4070
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. cruchagac@wustl.edu.ORCID http://orcid.org/0000-0002-0276-2899
Funding
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MSmartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5MImaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9MThe natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5MResearch Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI Susan Lynn Stark · 2020 to 2026
$28.7MIdentification and Characterization of Cell-Specific Transposable Elements Implicated on Alzheimer Disease and Healthy AgingR01AG078964 · NIA · WASHINGTON UNIVERSITY · PI Carlos Cruchaga, Bess Frost · 2022 to 2026
$9.0MGenetic Architecture of Alzheimer’s disease ProteinopathiesR01AG064877 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CRUCHAGA, CARLOS, KAMBOH, M. ILYAS · 2021 to 2024
$8.4MVCID Center Without Walls for Understanding and Leveraging Small Vessel Cerebrovascular Disease Mechanisms in ADRDRF1NS139970 · NINDS · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS, GOYAL, MANU S · 2024 to 2024
$4.4MUSING QUANTITATIVE TRAITS TO IDENTIFY NOVEL GENES FOR ALZHEIMERS DISEASE AND OTHER COMPLEX TRAITSRF1AG053303 · NIA · WASHINGTON UNIVERSITY · PI CLIMER, SHARLEE, CRUCHAGA, CARLOS · 2016 to 2020
$4.0MGenomic and Metabolomic Data Integration in a Longitudinal Cohort at Risk for Alzheimer's DiseaseRF1AG054047 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI ENGELMAN, CORINNE D. · 2022 to 2025
$3.8MGenomic and Metabolomic Data Integration in a Longitudinal Cohort at Risk for Alzheimer's DiseaseR01AG054047 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI ENGELMAN, CORINNE D. · 2016 to 2020
$3.6MGENETIC MODIFIERS OF CEREBROSPINAL FLUID TREM2 IN ALZHEIMER'S DISEASERF1AG058501 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS, PICCIO, LAURA · 2018 to 2018
$3.5MNIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P30 AG066444NIA NIH HHS R01 AG044546NIA NIH HHS R01 AG054047NIA NIH HHS R01 AG058501NIA NIH HHS R01 AG064877NIA NIH HHS R01 AG074007NIA NIH HHS R01 AG078964NIA NIH HHS R01 AG089239NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG054047NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG074007NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG058922NIA NIH HHS U19 AG032438NINDS NIH HHS K23 NS110927NINDS NIH HHS RF1 NS139970U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG044546
Abstract
Brain metabolism perturbation can contribute to traits and diseases. We conducted a genome-wide association study for cerebrospinal fluid (CSF) and brain metabolite levels, identifying 205 independent associations (47.3% new signals, containing 11 new loci) for 139 CSF metabolites, and 32 independent associations (43.8% new signals, containing 4 new loci) for 31 brain metabolites. Of these, 96.9% (CSF) and 71.4% (brain) of the new signals belonged to previously analyzed metabolites in blood or urine. We integrated the metabolite quantitative trait loci (MQTLs) with 23 neurological, psychiatric and common human traits and diseases through colocalization to identify metabolites and biological processes implicated in these phenotypes. Combining CSF and brain, we identified 71 metabolite-trait associations, such as glycerophosphocholines with Alzheimer's disease, O-sulfo-L-tyrosine with Parkinson's disease, glycine, xanthine with waist-to-hip ratio and ergothioneine with inflammatory bowel disease. Our study expanded the knowledge of MQTLs in the central nervous system, providing insights into human traits.
Indexed as
Alzheimer DiseaseBrainGenome-Wide Association StudyQuantitative Trait LociGlycineHumansMaleMetabolomeParkinson DiseasePhenotypePolymorphism, Single NucleotideTyrosineWaist-Hip RatioXanthineGlycineTyrosineXanthine
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