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Global, Local Polynesian Ancestry Influence Disease Risk Among Native Hawaiians

NEW YORK – Higher levels of Polynesian ancestry may lead to a higher risk of obesity, type 2 diabetes, and heart failure among Native Hawaiians, a new study has found.

Native Hawaiians have higher rates of a number of chronic health conditions compared to other people living in Hawaii. For a new study appearing in PLOS Genetics, researchers from the University of Southern California and elsewhere set out to identify genetic risk factors that may influence the health of Native Hawaiians, who have been understudied in genetic analyses.

Drawing on a cohort of 4,000 Native Hawaiians, the researchers found that for every 10 percent increase in Polynesian ancestry — which likely encompasses genetic, lifestyle, and environmental risk factors — Native Hawaiians had a more than 8 percent rise in type 2 diabetes risk and 11 percent increase in heart failure risk. They further homed in on a region of chromosome 6 associated with type 2 diabetes that appears to be more common among people of Polynesian descent.

Studies like these could help identify population-specific genetic susceptibility factors and inform medical care, the researchers added. "The underlying contributors to this apparent association between ancestry and risk are likely both genetic and environmental factors that correlate with Polynesian ancestry," senior author Charleston Chiang, an assistant professor of preventive medicine and quantitative and computational biology at USC, said in an email. 

"Our study implies that risk assessment in the clinic could take this into account when devising a treatment or prevention plan, and modifiable risk factors can be managed via intervention to improve the care of this population," Chiang added.

As there is no publicly available reference panel for Polynesian ancestry, the researchers developed one based on a cohort of 3,940 self-identified Native Hawaiians from the Multiethnic Cohort. Native Hawaiians today are an admixed population with Polynesian, European, Asian, and African ancestry components, and the researchers stressed that genetics should not be used to define someone's community membership.

Within this cohort of 3,940 Native Hawaiians, the researchers identified 178 individuals with the highest estimated amount of Polynesian ancestry, more than 90 percent, to develop the panel. Using this reference panel, they then estimated the global genetic ancestry of the remaining 3,762 individuals from the Multiethnic Cohort.

They examined whether Polynesian ancestry was associated with risk of obesity, type 2 diabetes, and cardiovascular disease — three conditions epidemiological studies have indicated Native Hawaiians are at increased risk of developing — and related phenotypes like body-mass index and cholesterol levels.

Overall, they found Polynesian ancestry was strongly associated with increased risk of obesity, type 2 diabetes, and heart failure, as well as with higher BMI and lower HDL levels. In particular, they noted that every 10 percent increase in Polynesian ancestry was associated with an 8.6 percent increase in type 2 diabetes risk and 11 percent increase in heart failure risk, as well as with a 0.35-unit increase in BMI.

Using admixture mapping, the researchers also examine local genetic ancestry within their cohort and its ties to cardiometabolic traits. They homed in on a region on chromosome 6 that was linked to type 2 diabetes, identifying two variants there. One of these variants — rs370140172 — was more common among Native Hawaiians, about 11.2 percent prevalence, than among other continental populations, in which it was either not found or found at less than 1 percent prevalence.

The findings could help to understand the risk Native Hawaiians face for these and other conditions. 

Chiang added that he and his lab are working to develop additional genomic resources, similar to ones available for European or East Asian populations, to better understand how these genetic risk factors contributed to disease. "Not only would this help illuminate Polynesian-specific genetic risk factors, but also potentially allow a window to understand the biology behind these complex diseases that may not be available in a Euro-centric study," he said.

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