# An evolutionary framework to elucidate and interpret the genetic architecture of complex traits in diverse populations  - diversity supplement

> **NIH NIH R35** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $12,799

## Abstract

Project Summary / Abstract (from Parent Grant)
Both environmental and genetic factors contribute to disparity in disease risks between populations. The genetic
causes of differences between populations are intimately tied to the evolutionary histories of these populations.
Therefore, a better incorporation of evolutionary thinking will help explain the disparity among diverse populations
today and improve clinical practices and personalized care. To this end, the Chiang Lab will continue to develop
an integrative framework combining evolutionary population genetics with genetic epidemiology in humans,
utilizing both empirical data analysis and quantitative methods development to better probe into the genetic
architecture of complex traits within and between populations. This integrative framework consists of three main
foci: (1) the genetic architecture of human complex traits, (2) the demographic history, and (3) the adaptive
history of human populations. Research in the first topic informs the genetic consequences on our phenome
today, while research in the latter two explains the evolutionary mechanisms through which variation arise within
and between human populations. More importantly, research from the Chiang Lab focuses not solely on these
topics, but also leverages information on one to inform the other. Within this paradigm, the Chiang Lab will focus
on the following three goals over the next five years. First, we will execute a comprehensive genetic research
program to address the health disparities in Native Hawaiians. Specifically, we will generate the genomic
resources necessary to accelerate genetic research in this population. We will then characterize the
demographic history of the Native Hawaiians to illustrate the benefit of conducting genomic studies in
understudied populations, perform large-scale meta-analysis in Polynesian populations to identify population-
specific alleles associated with diseases prevalent in Native Hawaiians, and engage the Native Hawaiian
community for future partnership and collaborations. Second, we will investigate the evolutionary etiology for
elevated risk in present-day populations. Using Latino populations as an example, we will examine if the elevated
risk in childhood leukemia in this population is due to the selective pressure introduced during European contact
in the 16th century. Third, we will revolutionize the current concept of genetic relatedness by introducing a new
genetic similarity matrix among individuals that incorporates information from the genealogical tree of the
population. This matrix will improve the performance of a number of statistical genetic applications, such as
heritability estimation and phenotype imputation. While we used Native Hawaiians and Latinos as example
populations in this proposal, this integrated framework of genetic epidemiology and evolution will also benefit
future research in other understudied ethnic minorities. We are uniquely positioned to achieve t...

## Key facts

- **NIH application ID:** 10539156
- **Project number:** 3R35GM142783-01S1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Charleston Chiang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $12,799
- **Award type:** 3
- **Project period:** 2021-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10539156

## Citation

> US National Institutes of Health, RePORTER application 10539156, An evolutionary framework to elucidate and interpret the genetic architecture of complex traits in diverse populations  - diversity supplement (3R35GM142783-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10539156. Licensed CC0.

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