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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
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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.
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.

  1. 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
  2. Brain and blood metabolome for Alzheimer's dementia: findings from a targeted metabolomics analysis. Huo Z, et al. Neurobiology of aging. 2020. PMID: 31785839
  3. DNA methylation variability in Alzheimer's disease. Huo Z, et al. Neurobiology of aging. 2019. PMID: 30660039
  4. Identifying Multi-Omics Causers and Causal Pathways for Complex Traits. Qin H, et al. Frontiers in genetics. 2019. PMID: 30847004
  5. Identifying Rare Variant Associations in Admixed Populations. Qin H, et al. Scientific reports. 2019. PMID: 30931973