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Description

The majority of metabolite quantitative trait loci (MQTL) were discovered using blood and urine tissues. This data represents the first large-scaled CSF and brain study, which will advance the understanding of genetic regulation in metabolite levels by identifying novel MQTLs. For 440 CSF metabolites, meta-analysis was performed using 2,311 non-related non-Hispanic white individuals from Knight-ADRC, DIAN, ADNI, Fundacio ACE, and Barcelona-1, together with a previous CSF study (N=291). For 962 brain metabolites, meta-analysis in the European ancestry was performed using 405 WashU individuals, 415 ROSMAP individuals, and 196 MAYO individuals. The healthy control individuals accounted for 35% of CSF and 25% of brain individuals in the studies, and the rest individuals either was diagnosed with a type of dementia or showed sign of neurodegeneration.  The dataset consists of GWAS summary statistics (GRCh38) calculated for each of 440 CSF metabolites and 962 brain metabolites measured by Metabolon (HD4) platform.

Available Filesets

NameAccessionLatest ReleaseDescription
KGAD MQTL: Brain metabolite data P-values only (open access)fsa000049NG00131.v1Brain metabolite data P-values only
KGAD MQTL: Full brain metabolite data (application needed)fsa000050NG00131.v1Full brain metabolite data
KGAD MQTL: CSF metabolite data P-values only (open access)fsa000051NG00131.v1CSF metabolite data P-values only
KGAD MQTL: Full CSF metabolite data (application needed)fsa000052NG00131.v1Full CSF metabolite data

View the File Manifest for a full list of files released in this dataset.

Consent LevelNumber of Subjects
DS-ADRD-IRB-PUB-NPUNA

Visit the Data Use Limitations page for definitions of the consent levels above.

Total number of approved DARs: 1
  • Investigator:
    Zhao, Jinying
    Institution:
    University of Florida
    Project Title:
    Identifying novel biomarkers for human complex diseases using an integrated multi-omics approach
    Date of Approval:
    November 21, 2023
    Request status:
    Approved
    Research use statements:
    Show statements
    Technical Research Use Statement:
    GWAS, WES and WGS have identified many genes associated with Alzheimer’s Dementia (AD) and its related traits. However, the identified genes thus far collectively explain only a small proportion of disease heritability, suggesting that more genes remained to be identified. Moreover, there is a clear gender and ethnic disparity for AD susceptibility, but little research has been done to identify gender- and ethnic-specific variants associated with AD. Of the many challenges for deciphering AD pathology, lacking of efficient and power statistical methods for genetic association mapping and causal inference represents a major bottleneck. To tackle this challenge, we have developed a set of novel statistical and bioinformatics approaches for genetic association mapping and multi-omics causation inference in large-scale ethnicity-specific epidemiological studies. The goal of this project is to leverage the multi-omics and clinical data archived by the ADSP, ADNI, ADGC as well as other AD-related data repositories to identify novel genes and molecular markers for AD. Specifically, we will (1) validate our novel methods for identifying novel risk and protective genomic variants and multi-omics causal pathways of AD; (2) identify novel ethnicity- and gender-specific genes and molecular causal pathways of AD. We will share our results, statistical methods and computational software with the scientific community.
    Non-Technical Research Use Statement:
    Although many genes have been associated with Alzheimer’s Dementia (AD), these genes altogether explain only a small fraction of disease etiology, suggesting more genes remained to be identified. Of the many challenges for deciphering AD pathology, lacking of power statistical methods represents a major bottleneck. To tackle this challenge, we have developed a set of novel statistical and bioinformatics approaches for genetic association mapping and multi-omics causation inference in large-scale ethnicity-specific epidemiological studies. The goal of this project is to leverage the rich genetic and other omic data along with clinical data archived by the ADSP, ADNI, ADGC as well as other AD-related data repositories to identify novel genes and molecular markers for AD. Such results will enhance our understanding of AD pathogenesis and may also serve as biomarkers for early diagnosis and therapeutic targets.

Acknowledgment statement for any data distributed by NIAGADS:

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

Use the study-specific acknowledgement statements below (as applicable):

For investigators using any data from this dataset:

Please cite/reference the use of NIAGADS data by including the accession NG00131.

For investigators using Large scale pQTL and mQTL atlas in brain and CSF (sa000031) data:

For use of data in Large scale CSF proteogenomic atlas (ng00130):

We thank all the participants and their families, as well as the many involved institutions and their staff.

This work was supported by grants from the National Institutes of Health (R01AG044546 (CC), P01AG003991 (CC, JCM), RF1AG053303 (CC), RF1AG058501 (CC), U01AG058922 (CC), RF1AG074007 (YJS), R00AG062723 (LI), P30 AG066515 (TWC, MDG), the Chan Zuckerberg Initiative (CZI), the Michael J. Fox Foundation (LI, CC), the Department of Defense (LI- W81XWH2010849), the Alzheimer’s Association Zenith Fellows Award (ZEN-22-848604, awarded to CC), and the Bright Focus Foundation (A2021033S, LI).

GSK provided funding to support the analyses performed in this study.

The recruitment and clinical characterization of research participants at Washington University were supported by NIH P30AG066444 (JCM), P01AG03991 (JCM), and P01AG026276 (JCM).

This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, the NeuroGenomics and Informatics Center (NGI: https://neurogenomics.wustl.edu/) and the Departments of Neurology and Psychiatry at Washington University School of Medicine.

Data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer Network (DIAN, U19AG032438) funded by the National Institute on Aging (NIA), the Alzheimer’s Association (SG-20- 690363-DIAN), the German Center for Neurodegenerative Diseases (DZNE), Raul Carrea Institute for Neurological Research (FLENI), Partial support by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development, AMED, the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), Spanish Institute of Health Carlos III (ISCIII), Canadian Institutes of Health Research (CIHR), Canadian Consortium of Neurodegeneration and Aging, Brain Canada Foundation, and Fonds de Recherche du Québec Santé.

Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

For use of data in Large scale genetics study on CSF and brain metabolite levels (ng00131):

We thank all the participants and their families, as well as the many involved institutions and their staff.

This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, the Neurogenomics and Informatics Center (NGI: https://neurogenomics.wustl.edu/)and the Departments of Neurology and Psychiatry at Washington University School of Medicine.

DIAN resources: Data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer Network (DIAN, U19AG032438) funded by the National Institute on Aging (NIA), the Alzheimer’s Association (SG-20-690363-DIAN), the German Center for Neurodegenerative Diseases (DZNE), Raul Carrea Institute for Neurological Research (FLENI), Partial support by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development, AMED, the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), Spanish Institute of Health Carlos III (ISCIII), Canadian Institutes of Health Research (CIHR), Canadian Consortium of Neurodegeneration and Aging, Brain Canada Foundation, and Fonds de Recherche du Québec Santé. This manuscript has been reviewed by DIAN Study investigators for scientific content and consistency of data interpretation with previous DIAN Study publications. We acknowledge the altruism of the participants and their families and contributions of the DIAN research and support staff at each of the participating sites for their contributions to this study.

ADNI acknowledgement: Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

AMP-AD Acknowledgements: The results published here are in whole or in part based on data obtained from the AD Knowledge Portal (https://adknowledgeportal.org). This work was done as part of the National Institute on Aging's Accelerating Medicines Partnership Program for Alzheimer's Disease (AMP-AD) and was supported by NIH grants 1U19AG063744, 1R01AG069901-01A1, U01AG061357, P30AG10161, P30AG72975, R01AG15819, R01AG17917, U01AG46152, U01AG61356, RF1AG058942, RF1AG059093, and U01AG061359. The Religious Orders and the Rush Memory and Aging studies were supported by the National Institute on Aging grants P30AG10161, R01AG15819, R01AG17917, U01AG46152, and U01AG61356. The NIA also supported the Alzheimer Disease Metabolomics Consortium, which is a part of the NIA's national initiatives AMP-AD and M2OVE-AD (R01 AG046171, RF1 AG051550, and 3U01 AG061359-02S1). We thank the participants of ROS and MAP for their essential contributions and the gifts of their brains to these projects. All subjects gave informed consent. The Mayo Clinic samples are part of the RNAseq study data led by Dr. Nilüfer Ertekin-Taner, Mayo Clinic, Jacksonville, FL as part of the multi-PI U01 AG046139 (MPIs Golde, Ertekin-Taner, Younkin, Price). Samples were provided from the following sources: The Mayo Clinic Brain Bank. Data collection was supported through funding by NIA grants P50 AG016574, R01 AG032990, U01 AG046139, R01 AG018023, U01 AG006576, U01 AG006786, R01 AG025711, R01 AG017216, R01 AG003949, NINDS grant R01 NS080820, CurePSP Foundation, and support from Mayo Foundation.

ACE Alzheimer Center acknowledgement: A. Cano received support from the Spanish Ministry of Science, Innovation and Universities under the grant Juan de la Cierva (FJC2018-036012-I) and Instituto de Salud Carlos III (ISCIII) under the grant Sara Borrell (CD22/00125). AC is also funded by the Spanish Ministry of Science and Innovation, Proyectos de Generación de Conocimiento (PID2021-122473OA-I00). P. García-González is supported by CIBERNED employment plan (CNV-304-PRF-866). Authors acknowledge the support of the Acción Estratégica en Salud, integrated in the Spanish National R + D + I Plan and financed by ISCIII Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER “Una manera de hacer Europa") grants PI17/01474, PI19/00335, PI22/01403 and PI22/00258. A.R. is also supported by ISCIII national grant PMP22/00022, funded by the European Union (NextGenerationEU). The support of CIBERNED (ISCIII) under the grants CB06/05/2004 and CB18/05/00010. The support from PREADAPT project, Joint Program for Neurodegenerative Diseases (JPND) grant Nº AC19/00097, from HARPONE project, Agency for Innovation and Entrepreneurship (VLAIO) grant Nº PR067/21, from ADAPTED project, the EU/EFPIA Innovative Medicines Initiative Joint Undertaking Grant Nº 115975, and from DESCARTES project, German Research Foundation (DFG). The support of Fundación bancaria “La Caixa” and Grífols SA (GR@ACE project).

Wisconsin Acknowledgement: Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Number R01AG054047.