Alzheimer's disease in native hawaiians and pacific islanders: sample acquisition and whole genome sequencing

The National Institute on Aging awarded Brigham Young University $5.477 million under Cooperative Agreement U01AG090346 on September 15, 2025, to recruit and sequence 5,000 Native Hawaiian and Pacific Islander participants for Alzheimer's disease research under the Aging Research program (CFDA 93.866).

The project will conduct whole genome sequencing, SNP array genotyping, and standard laboratory assays on blood samples collected from 1,000 participants annually over five years. Each participant will complete comprehensive health, medical, social determinants of health, diet, and physical activity surveys; receive neuropsychological assessment using the National Alzheimer's Coordinating Center battery with cultural adaptations; and undergo diagnostic adjudication. The work addresses documented underrepresentation of Native Hawaiians and Pacific Islanders in Alzheimer's disease research repositories and preliminary evidence suggesting unique genetic architecture for AD in these populations, including absence of correlation between APOE SNPs and AD status in Chamorros and Polynesians.

Performance occurs in Utah through August 31, 2031. Four sub-recipients deliver specialized functions: University of Miami's Center for Genome Technology will conduct whole genome genotyping-array analysis on all 5,000 samples at 1,000 per year, with data quality control and delivery to project leaders and the NIAGADS repository; the University of Pennsylvania's NIAGADS repository will manage phenotype, genotype, and sequence data sharing, receive and archive project results, and manage qualified-access community release and dbGaP integration; Utah State University will develop diagnostic protocols, train staff at both USU and BYU sites, conduct diagnostic case conferences, and assist with dataset creation and manuscript preparation; and Indiana University's genetics biobank will develop biospecimen collection and request procedures, assemble kits, receive and process specimens, maintain storage, distribute samples to designated labs, and provide quality control reporting.

Abstract

Alzheimer's disease (ad) is among the most significant public health and medical challenges of our day. Approximately 7 million americans are living with ad, and without effective interventions, the number will double in the next 25 years. Homogenous datasets limit the clinical utility of discoveries, possibly leading to race-based disparities in therapeutics and diagnostic tools. Almost all ad research data were derived from majority-white populations in high-income countries. Native hawaiians and pacific islanders (nhpis) have exceptionally high risk. Yet, despite being the second fastest-growing racial minority group, nhpis are the least represented racial minority group in large repositories/datasets. The adsp was initiated, in part, to solve the genetic architecture of ad. While limited data exist, available evidence suggests that the genetic architecture of ad in nhpis is unique. For example, the apoe snps are not correlated with ad in chamorros or polynesians. We plan to do the following. Aim 1. Recruit and collect data from 5,000 nhpis. We will recruit 1,000 nhpis annually through our network of connections, including community and religious leaders, social media, radio, TV, personal connections, and word of mouth. Each participant will complete thorough health, medical, social determinants of health, diet, physical activity, and demographics surveys; a neurophysical exam; provide a blood sample; and ad testing. We will collect whole genome sequences, SNP array data, and standard laboratory assays for each participant. Aim 2. Participant diagnosis. Each participant will be diagnosed using the nacc battery and adjudicated following the protocols established by acad with minor adaptations to make the assessments culturally appropriate for nhpis. Aim 3. Genetic analyses. We will describe nhpi genetics (e.g., estimate SNP frequencies in nhpis), analyze nhpi population structure, and conduct the first ad gwas in nhpis.