Leveraging the Evolutionary History to Improve Identification of Trait-Associated Alleles and Risk Stratification Models in Native Hawaiians
Project Number5R01HG011646-03
Former Number1R01HG011646-01
Contact PI/Project LeaderCHIANG, CHARLESTON
Awardee OrganizationUNIVERSITY OF SOUTHERN CALIFORNIA
Description
Abstract Text
Project Summary / Abstract
Native Hawaiians are one of the most understudied, ethnic minority population in the United States. Compared
to their European or Asian American counterparts, Native Hawaiians exhibit alarming rates of obesity, diabetes,
and other related chronic health conditions, even after adjusting for common modifiable risk factors. Yet few
genetic research has focused on Native Hawaiians. Genomic resources such as imputation reference panels
are also generally lacking for Native Hawaiians, preventing comprehensive genetic investigations to be
undertaken with this population. Therefore, compared to other continental populations, Native Hawaiians are not
on pace to reap the benefits we have gained from large scale genomic studies of diseases.
While there are growing recognitions of the need to include more non-European individuals in genomic
studies, an often-ignored fact is that the disease risks for members of a population are intimately tied to the
evolutionary history of that population. Theoretical and empirical studies have shown that the demographic
history of a population will impact the genotype-phenotype relationship in ways specific to that population.
Therefore, a better incorporation of evolutionary thinking will help better understand the genetic basis for
differences in disease risk among diverse populations today. To this end, we are proposing to develop an
integrative framework that combines principles of both population genetics and genetic epidemiology to
understand why Native Hawaiians show excess risk in obesity and type-2 diabetes (T2D). Specifically, by
leveraging newly generated whole genome sequences (WGS) and existing array genotype data on >5,600
Native Hawaiians, we will first characterize the demographic history of the Native Hawaiians and the impact of
this history to the enrichment of functional alleles. These alleles are likely under natural selection, important for
the health of Native Hawaiians, but would be easily missed if one only studies other continental populations that
exist in large number. Secondly, by combining with existing WGS from Samoans, we will construct the first
Polynesian-specific imputation reference panel. We will then impute and conduct the largest association study
to date in >10,000 Polynesian individuals and >2,000 Micronesian individuals for obesity and T2D. Thirdly, we
will evaluate the transferability of risk stratification models for obesity and T2D based on polygenic risk scores
(PRS) in Native Hawaiians, determine the population genetic and non-genetic factors that may have contributed
to the expected poor transferability of these models, and assess if Polynesian-specific summary statistics will
improve the risk stratification models. Finally, we will conduct pilot studies in the form of focus groups to
understand the concerns Native Hawaiian community may have in future participation of genomic research. The
results from this proposal will help motivate and guide the design of future genomic studies in this understudied
population, identify population-specific alleles influencing obesity and T2D, and improve future risk stratification
models of diseases in Native Hawaiians and other Polynesian populations.
Public Health Relevance Statement
Project Narrative
Our study will identify population-specific risk alleles and improve the risk stratification models for obesity and
type-2 diabetes in Native Hawaiians. Moreover, we will reach out to members of the Native Hawaiian community
to understand their concerns of participating in genomic research. Together, our research will improve our
understanding of genetic risk factors in human complex diseases, provide much needed genomic resources to
accelerate future studies, and also provide guidance to the design of future genomic studies in this understudied
and underserved population.
No Sub Projects information available for 5R01HG011646-03
Publications
Publications are associated with projects, but cannot be identified with any particular year of the project or fiscal year of funding. This is due to the continuous and cumulative nature of knowledge generation across the life of a project and the sometimes long and variable publishing timeline. Similarly, for multi-component projects, publications are associated with the parent core project and not with individual sub-projects.
No Publications available for 5R01HG011646-03
Patents
No Patents information available for 5R01HG011646-03
Outcomes
The Project Outcomes shown here are displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed are those of the PI and do not necessarily reflect the views of the National Institutes of Health. NIH has not endorsed the content below.
No Outcomes available for 5R01HG011646-03
Clinical Studies
No Clinical Studies information available for 5R01HG011646-03
News and More
Related News Releases
No news release information available for 5R01HG011646-03
History
No Historical information available for 5R01HG011646-03
Similar Projects
No Similar Projects information available for 5R01HG011646-03