Identifying novel biomarkers for human complex diseases using an integrated multi-omics approach
- PI
- Zhao, Jinying
- DAR ID
- 10065
- Initial Approval Date
- March 19, 2019
- Current DAR Status
- Closed
- PI Institution
- University of Florida
- PI Institution Country
- United States
- PI Institution Type
- Non-Profit
Requested Datasets (18)
NG00067Alzheimer's Disease Sequencing Project Umbrella StudyNG00108Profiling microglia expression profiles in AD using single-nuclei RNA-seqNG00105MiGA – Microglia Genomic AtlasNG00106LASI-DAD Genotyping Chip Data (Illumina Infinium GSA-24 v2.0), Imputed Data (1000 Genomes Phase 3 v5 and TOPMed r2)NG00113Metabolomic and lipidomic signatures in Alzheimer disease brainsNG00114DNA Methylation in Alzheimer disease brainsNG00104Dataset from Clinical and Pathological Studies in the Oldest Old (90+ Study)NG00119Health and Retirement Study Genotype Data 2006-2012NG00121Alzheimer’s disease single-neuron whole-genome sequencing - Miller 2022NG00117NCRAD Families GWASNG00127A longitudinal study of Alzheimer's Disease and other dementing illnesses – KnightADRC GWASNG00126A fast and robust strategy to remove variant level artifacts in Alzheimer’s Disease Sequencing Project data (Belloy et al. 2022)
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NG00132Health and Retirement Study (HRS) APOE and Serotonin Transporter AllelesNG00118AMP-AD SV WGS and SV-xQTLNG00134National Health and Aging Trends Study (NHATS) GWASNG00130Large scale CSF proteogenomic atlasNG00144The Prediction of Alzheimer’s Disease through Multi-Trait Genetic ModelingNG00131Large scale genetics study on CSF and brain metabolite levels
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 Summary
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.
Reported Publications (5)
Publications shown are those reported by investigators through NIAGADS DAR reporting and renewal processes and may not represent a complete list of publications associated with the project.
- Fine-mapping and replication of EWAS loci harboring putative epigenetic alterations associated with AD neuropathology in a large collection of human brain tissue samples. Palma-Gudiel H, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2023. PMID: 35959851
- Brain and blood metabolome for Alzheimer's dementia: findings from a targeted metabolomics analysis. Huo Z, et al. Neurobiology of aging. 2020. PMID: 31785839
- DNA methylation variability in Alzheimer's disease. Huo Z, et al. Neurobiology of aging. 2019. PMID: 30660039
- Identifying Multi-Omics Causers and Causal Pathways for Complex Traits. Qin H, et al. Frontiers in genetics. 2019. PMID: 30847004
- Identifying Rare Variant Associations in Admixed Populations. Qin H, et al. Scientific reports. 2019. PMID: 30931973