Background: Current understanding of blood pressure (BP) phenotypes has come mainly from studies in European-ancestry populations; limited effort has focused on Polynesian populations, whose unique population history has provided insight into the biological foundations of many complex traits including obesity and lipid level variation. Here, we performed genome-wide association studies of 5 BP traits – systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), and hypertension (HTN) – in a sample of 3,043 Samoan participants.

Methods: Genotypes were measured from two sources. First, 659,492 variants were genotyped on an Affymetrix 6.0 array. Then, we imputed an additional 9,619,694 variants using a Samoan-specific haplotype reference panel derived from 1,284 Samoan individuals whole-genome sequenced through the TOPMed program. We then performed association testing of inverse-normally transformed traits using linear/logistic mixed modeling adjusting for fixed effects of age, sex, principal components of ancestry derived through PC-AiR and a kinship random effect derived from PC-Relate.

Results: While no variants were genome-wide significant, we observed 15 unique loci associated with blood pressure phenotypes at p < 1E-6. Notable among these, variants in FBXO32 were associated with PP (p = 9.2E-7); heterozygous individuals of the sentinel variant rs62521280 had an unadjusted mean PP of 62.4 vs. 46.6 mmHg for homozygous reference individuals. The protein encoded by FBXO32 is highly expressed during muscle atrophy, and Fbxo32 knockout mice had decreased susceptibility to induced muscular atrophy. Additionally, many variants in TOP1MT were associated with DBP and MAP, including a missense variant, rs2293925 (DBP p = 6.4E-7 and MAP p = 5.1E-7). The mouse Top1mt knockout model has abnormal autophagy and abnormal blood homeostasis phenotypes. Additionally, we observed association in three loci

(ATOX1, CASC15, and GIPR) that have been associated with cardiovascular phenotypes in other studies.

Conclusions: We observed several known and novel genetic loci associated with BP in Samoans suggesting that while some genetic architecture of blood pressure phenotypes is shared across ancestries, there may be unique associations within Polynesians. We are currently investigating potential associations between these loci and BP phenotypes in an independent cohort of Samoan adults. Additional studies will be necessary to validate these associations and to determine the underpinnings of these associations, which may point to previously unknown biological mechanisms of cardiovascular health.