The impact of global and local Polynesian genetic ancestry on complex traits in Native Hawaiians
Open Access
- 11 February 2021
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Genetics
- Vol. 17 (2), e1009273
- https://doi.org/10.1371/journal.pgen.1009273
Abstract
Epidemiological studies of obesity, Type-2 diabetes (T2D), cardiovascular diseases and several common cancers have revealed an increased risk in Native Hawaiians compared to European- or Asian-Americans living in the Hawaiian islands. However, there remains a gap in our understanding of the genetic factors that affect the health of Native Hawaiians. To fill this gap, we studied the genetic risk factors at both the chromosomal and sub-chromosomal scales using genome-wide SNP array data on ~4,000 Native Hawaiians from the Multiethnic Cohort. We estimated the genomic proportion of Native Hawaiian ancestry (“global ancestry,” which we presumed to be Polynesian in origin), as well as this ancestral component along each chromosome (“local ancestry”) and tested their respective association with binary and quantitative cardiometabolic traits. After attempting to adjust for non-genetic covariates evaluated through questionnaires, we found that per 10% increase in global Polynesian genetic ancestry, there is a respective 8.6%, and 11.0% increase in the odds of being diabetic (P = 1.65×10−4) and having heart failure (P = 2.18×10−4), as well as a 0.059 s.d. increase in BMI (P = 1.04×10−10). When testing the association of local Polynesian ancestry with risk of disease or biomarkers, we identified a chr6 region associated with T2D. This association was driven by an uniquely prevalent variant in Polynesian ancestry individuals. However, we could not replicate this finding in an independent Polynesian cohort from Samoa due to the small sample size of the replication cohort. In conclusion, we showed that Polynesian ancestry, which likely capture both genetic and lifestyle risk factors, is associated with an increased risk of obesity, Type-2 diabetes, and heart failure, and that larger cohorts of Polynesian ancestry individuals will be needed to replicate the putative association on chr6 with T2D. Native Hawaiians are one of the fastest growing ethnic minorities in the U.S., and exhibit increased risk for metabolic and cardiovascular diseases. However, they are generally understudied, especially from a genetic perspective. To fill this gap, we studied the association of Polynesian genetic ancestry, at genomic and subgenomic scales, with quantitative and binary traits in self-identified Native Hawaiians. We showed that Polynesian ancestry, which likely captures both genetic and non-genetic risk factors related to Native Hawaiian people and culture, is associated with increased risk for obesity, type-2 diabetes, and heart failure. While we do not endorse utilizing genetic information to supplant current standards of defining community membership through self-identity or genealogical records, our results suggest future studies could identify population-specific genetic susceptibility factors that may elucidate underlying biological mechanisms and reducing the disparity in disease risks in Polynesian populations.Keywords
This publication has 53 references indexed in Scilit:
- Population Genetic Structure and Origins of Native Hawaiians in the Multiethnic Cohort StudyPLOS ONE, 2012
- Dysfunctional Adiposity and the Risk of Prediabetes and Type 2 Diabetes in Obese AdultsJAMA, 2012
- More Than Black and White: Differences in Predictors of Obesity Among Native Hawaiian/Pacific Islanders and European AmericansObesity, 2012
- The landscape of recombination in African AmericansNature, 2011
- Robust relationship inference in genome-wide association studiesBioinformatics, 2010
- Self-reported ethnicity, genetic structure and the impact of population stratification in a multiethnic studyHuman Genetics, 2010
- Variance component model to account for sample structure in genome-wide association studiesNature Genetics, 2010
- Cardiometabolic Health Disparities in Native Hawaiians and Other Pacific IslandersEpidemiologic Reviews, 2009
- Diabetes Incidence Based on Linkages With Health Plans: The Multiethnic CohortDiabetes, 2009
- EYS, encoding an ortholog of Drosophila spacemaker, is mutated in autosomal recessive retinitis pigmentosaNature Genetics, 2008