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

> **NIH NIH R35** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $393,531

## Abstract

Project Summary / Abstract
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 population 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 these
goals because of...

## Key facts

- **NIH application ID:** 10275367
- **Project number:** 1R35GM142783-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Charleston Chiang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $393,531
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10275367

## Citation

> US National Institutes of Health, RePORTER application 10275367, An evolutionary framework to elucidate and interpret the genetic architecture of complex traits in diverse populations (1R35GM142783-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10275367. Licensed CC0.

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