Meta-analysis of GWAS in Native Hawaiians and Polynesians identifies 25 trait loci for diabetes and obesity traits

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medRxiv Published May 12, 2026 Medically reviewed May 12, 2026 Study authors: Dinh, B. L.; Wang, X.; Sheng, X.; Wan, P.; Srivastava, A. K.; Naseri, T.; Viali, S.; Wilkens, L.; Le… DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider that genetic associations in Polynesian populations are limited and require larger, population-specific studies for validation.

This is a meta-analysis review that synthesized genome-wide association studies (GWAS) for Type 2 Diabetes and obesity traits in Native Hawaiians and Polynesian-ancestry populations. The scope included data from up to 8,461 individuals in Hawai'i and Samoa, using the TOPMed imputation panel and comparing results to multi-ethnic datasets from All-of-Us.

The authors synthesized findings of 25 trait-loci associations that met genome-wide significance. They confirmed a suspected association of the CREBRF variant with fasting glucose levels. However, novel loci-trait associations for BMI, LDL, and waist-hip ratio were not replicated in the multi-ethnic datasets.

Key limitations noted by the authors include the underrepresentation of global populations such as those from Polynesia. They also state that the lack of Polynesian-enriched findings outside the CREBRF locus informs the bounds of effect sizes or frequency of any enriched variants. The review calls for further expansion of cohort sizes and improved imputation references specific to these populations.

The practice relevance of these findings is not reported. The authors caution against inferring causation from association and against overstating the generalizability of findings to other populations.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

Although genome-wide association studies (GWAS) now routinely reveal genetic associations and biological insights in millions of individuals, underrepresentation of global populations, such as those from Polynesia, continue to persist. These exclusions, often driven by logistical challenges and lack of data, prevent systematic identification of population-enriched associations, such as the association of the missense variant at the CREBRF locus to BMI and type 2 diabetes discovered commonly occurring in Polynesian populations due to its rarity in global populations. Armed with the recently updated TOPMed imputation panel that could benefit studies in diverse populations that previously had poorer imputation performance, we performed the first GWAS of Native Hawaiians and largest to date of Polynesian-ancestry populations (combined N up to 8,461) to identify population-enriched associations for 13 adiposity and cardiometabolic traits available across both cohorts: BMI, fasting glucose, fasting insulin, HDL, height, hip circumference, HOMA-IR, LDL, T2D, total cholesterol, triglycerides, waist circumference, and waist-hip ratio. We found 25 trait-loci associations that met genome-wide significance: 20 previously reported or known associations and 5 associations newly confirmed via meta-analysis. In particular, with improved statistical power, we were able to confirm the suspected association between the missense CREBRF variant with fasting glucose levels. The remaining 4 potentially novel loci-trait associations for BMI, LDL, and waist-hip ratio, however, were not replicated in multi-ethnic datasets from All-of-Us despite having reasonable power to replicate. The lack of Polynesian-enriched findings outside of the CREBRF locus informs the bounds of the effect sizes or frequency of any enriched variants, and suggests that further expansion of cohort sizes from this region of the world and improved imputation references specific to these populations are needed to identify more population-enriched associations.