Polynesian ancestry study maps genetic links to 13 cardiometabolic traits

A meta-analysis of more than 8,000 Native Hawaiians and Samoans identified 25 genome-wide significant genetic associations across 13 adiposity and cardiometabolic traits, providing the largest genome-wide association study yet conducted in Polynesian-ancestry populations. Twenty of the associations were previously known or reported, while five were presented as potentially new links awaiting further validation.

The researchers combined data from Native Hawaiian and Samoan cohorts and used an updated TOPMed imputation reference panel, which can improve the analysis of genetic variation in populations that have been poorly represented in previous reference datasets. The study examined body mass index, fasting glucose, fasting insulin, HDL cholesterol, height, hip circumference, HOMA-IR, LDL cholesterol, type 2 diabetes, total cholesterol, triglycerides, waist circumference and waist-hip ratio. Its combined sample size reached 8,461 individuals.

One prominent result confirmed an association involving a missense variant at the CREBRF locus, where better statistical power strengthened evidence linking the variant to fasting glucose levels. CREBRF had previously been associated with body mass index and type 2 diabetes in Polynesian populations, where the relevant variant is uncommon globally. The analysis also reported four other potentially novel associations involving body mass index, LDL cholesterol and waist-hip ratio, but none of those four was replicated in the All of Us Research Program.

The findings indicate that the study did not uncover widespread additional genetic associations enriched specifically in Polynesian populations beyond CREBRF. According to the authors, this places bounds on the possible effect sizes or frequencies of population-enriched variants and highlights the need for larger cohorts and imputation reference panels tailored to Polynesian ancestry. Replication also remains important because a meta-analysis can identify statistically compelling associations that do not reproduce in an independent population. Overall, the work expands representation in genetic research while showing that the absence of additional discoveries should not be interpreted as proof that no other population-enriched effects exist.

Subject of Research: Genetic associations with adiposity and cardiometabolic traits in Native Hawaiian and Samoan populations

Article Title: Meta-analysis of over 8,000 individuals from Hawai‘i and Samoa for genetic associations to cardiometabolic phenotypes

Article References: Dinh, B. L., Wang, X., Sheng, X., Wan, P., Srivastava, A. K., Naseri, T., Viali, S., Wilkens, L., Le Marchand, L., Haiman, C., Weeks, D. E., Chiang, C. W. K., Carlson, J. C., & The Samoan Obesity, Lifestyle and Genetic Adaptations (OLaGA) Study Group (2026). Meta-analysis of over 8,000 individuals from Hawai‘i and Samoa for genetic associations to cardiometabolic phenotypes. PLOS Genetics, 22(10), e1012342. https://doi.org/10.1371/journal.pgen.1012342

Image Credits: AI Generated

DOI: 10.1371/journal.pgen.1012342

Keywords: GWAS, Polynesian ancestry, Native Hawaiians, Samoans, cardiometabolic traits, CREBRF, genetic associations, obesity, type 2 diabetes, TOPMed, Meta-analysis, over