# Integrating genome, other layers of omics, and non-genetic data to improve understanding of the etiology of human diseases in multi-ethnic populations

> **NIH NIH U54** · UNIVERSITY OF HAWAII AT MANOA · 2023 · $848,512

## Abstract

ABSTRACT
A variety of human disease show disparities across different populations and ethnic groups, such as Africans,
Hispanics/Latinos, Asians, Europeans, and Native Hawaiians. The etiology of many human diseases is not fully
understood, despite substantial efforts to identify associated non-genetic and genetic factors, including common
and rare genetic variants. More work focusing on different layers of omic markers including DNA methylation
(DNAm), gene, protein, and metabolite markers is urgently needed. Basic research supports the important roles
of certain CpG sites, genes, proteins, and metabolites in development of many diseases. Epidemiological studies
also have identified multiple candidate DNAm, gene, protein, and metabolite biomarkers for diseases/traits.
However, conventional epidemiologic studies were conducted primarily in individuals with European ancestry,
and it is unclear which DNAm/gene/protein/metabolite biomarkers identified to date are European ancestry-
specific or pan-ancestry. Also, findings with many of these biomarkers have been inconsistent, potentially due
to major methodological limitations, such as selection bias and uncontrolled confounding. There are critical
needs to apply a novel study design with reduced limitations of conventional biomarker studies for characterizing
causally related biomarkers in blood for human diseases across populations to improve our understanding of
disease etiology and reduce health disparities. One strategy to potentially decrease limitations of selection bias
and unmeasured confounding is to use genetic instruments for assessing the relationship between
DNAm/gene/protein/metabolite markers and diseases. Our preliminary work applying conventional methods to
develop genetic prediction models has revealed promising DNAm, gene, protein, and metabolite biomarkers in
blood associated with risk of several diseases in Europeans. The proposed project will apply a series of new
studies to address these important knowledge gaps. Specifically, we will 1) develop ethnic-specific DNAm, gene,
protein, and metabolite marker genetic prediction models in blood tissue across African Americans,
Hispanics/Latinos, Asian Americans, European Americans, and Native Hawaiians by applying novel methods
(Aim 1); 2) identify putative causal DNAm, gene, protein, and metabolite biomarkers in blood for risk of multiple
diseases across multi-ethnic populations by leveraging large scale genetic and non-genetic data (Aim 2); and 3)
evaluate potential interactions between known risk factors and predicted levels of established and newly
identified markers on risks of diseases of interest (Aim 3). Our study will generate important new knowledge for
substantially improving our understanding of the etiology of multiple human diseases across Africans,
Hispanics/Latinos, Asians, Europeans, and Native Hawaiians. The proposed new methods can also be applied
to other omic markers.

## Key facts

- **NIH application ID:** 10749846
- **Project number:** 1U54HG013243-01
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Lang Wu
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $848,512
- **Award type:** 1
- **Project period:** 2023-09-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10749846

## Citation

> US National Institutes of Health, RePORTER application 10749846, Integrating genome, other layers of omics, and non-genetic data to improve understanding of the etiology of human diseases in multi-ethnic populations (1U54HG013243-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10749846. Licensed CC0.

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