Improving imputation quality in Samoans through the integration of population-specific sequences into existing reference panels.

Genotype imputation is fundamental to association studies, and yet even gold standard panels like TOPMed are limited in the populations for which they yield good imputation. Specifically, Pacific Islanders are poorly represented in extant panels. To address this, we constructed an imputation reference panel using 1,285 Samoan individuals with whole-genome sequencing, combined with 1000 Genomes (1000G) samples, to create a reference panel that better represents Pacific Islander, specifically Samoan, genetic variation.

Patterns of urinary organophosphate ester metabolite trajectories in children: the HOME Study.

Background: Organophosphate esters (OPEs) have replaced flame retardant polybrominated diphenyl ethers as flame retardants in consumer products, but few longitudinal studies have characterized childhood OPE exposure.

Objective: We aimed to examine the exposure pattern of urinary OPE metabolites in children.

Methods: We quantified three urinary OPE metabolites five times in children (1, 2, 3, 5, 8 years) from 312 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio, USA.

A Polynesianspecific missense CETP variant alters the lipid profile.

Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at associate with serum lipid profiles and cardiovascular disease. Here, sequencing of identified a missense variant rs1597000001 (p.

Association of rs9939609 in FTO with BMI among Polynesian peoples living in Aotearoa New Zealand and other Pacific nations.

The fat mass and obesity associated (FTO) locus consistently associates with higher body mass index (BMI) across diverse ancestral groups. However, previous small studies of people of Polynesian ancestries have failed to replicate the association. In this study, we used Bayesian meta-analysis to test rs9939609, the most replicated FTO variant, for association with BMI with a large sample (n = 6095) of Aotearoa New Zealanders of Polynesian (Māori and Pacific) ancestry and of Samoan people living in the Independent State of Samoa and in American Samoa.

Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing.

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS.

Stable methylation loci are associated with systolic blood pressure in a Croatian island population.

The objective was to identify stable and dynamic DNA methylation loci associated with cardiometabolic traits among an adult population from the Croatian island of Hvar. An epigenome-wide association study was conducted using peripheral blood longitudinally collected at two time points 10 years apart via Infinium MethylationEPIC beadarray (n = 112). Stable and dynamic loci were identified using linear mixed models.

The association of sagittal abdominal diameter with metabolic syndrome risk before and after weight-loss surgery in adolescents.

Background: Metabolic syndrome (MetS) affects ∼10% of U.S. adolescents.

Multivariate analysis of a missense variant in CREBRF reveals associations with measures of adiposity in people of Polynesian ancestries.

The minor allele of rs373863828, a missense variant in CREB3 Regulatory Factor, is associated with several cardiometabolic phenotypes in Polynesian peoples. To better understand the variant, we tested the association of rs373863828 with a panel of correlated phenotypes (body mass index [BMI], weight, height, HDL cholesterol, triglycerides, and total cholesterol) using multivariate Bayesian association and network analyses in a Samoa cohort (n = 1632), Aotearoa New Zealand cohort (n = 1419), and combined cohort (n = 2976). An expanded set of phenotypes (adding estimated fat and fat-free mass, abdominal circumference, hip circumference, and abdominal-hip ratio) was tested in the Samoa cohort (n = 1496).

A stop-gain variant in is associated with atherogenic lipid profiles.

Current understanding of lipid genetics has come mainly from studies in European-ancestry populations; limited effort has focused on Polynesian populations, whose unique population history and high prevalence of dyslipidemia may provide insight into the biological foundations of variation in lipid levels. Here, we performed an association study to fine map a suggestive association on 5q35 with high-density lipoprotein cholesterol (HDL-C) seen in Micronesian and Polynesian populations. Fine-mapping analyses in a cohort of 2,851 Samoan adults highlighted an association between a stop-gain variant (rs200884524; c.

Gestational exposure to organophosphate esters and infant anthropometric measures in the first 4 weeks after birth.

Background: Few studies have examined whether gestational exposure to organophosphate esters (OPEs), widely used chemicals with potential endocrine-disrupting potency and developmental toxicity, is associated with impaired infant growth.

Methods: We analyzed data from 329 mother-infant pairs in the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006, Cincinnati, Ohio, USA). We quantified concentrations of four OPE metabolites in maternal urine collected at 16 and 26 weeks of gestation, and at delivery.

The missense variant, rs373863828, in CREBRF plays a role in longitudinal changes in body mass index in Samoans.

Objective: A missense variant, rs373863828, in CREBRF is associated with obesity in Polynesians. We investigate whether rs373863828 and other factors are associated with body mass index (BMI) rate-of-change between 2010 and 2017-19 in Samoans.

Methods: We used sex-stratified models to test whether BMI rate-of-change was associated with rs373863828, baseline BMI, age, residence, physical activity, and household asset score in a cohort study of 480 Samoan adults measured in both 2010 (mean age 43.

A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes.

Globally, autosomal recessive IFNAR1 deficiency is a rare inborn error of immunity underlying susceptibility to live attenuated vaccine and wild-type viruses. We report seven children from five unrelated kindreds of western Polynesian ancestry who suffered from severe viral diseases. All the patients are homozygous for the same nonsense IFNAR1 variant (p.

missense variant rs373863828 has both direct and indirect effects on type 2 diabetes and fasting glucose in Polynesian peoples living in Samoa and Aotearoa New Zealand.

Introduction: The minor allele of a missense variant, rs373863828, in is associated with higher body mass index (BMI), lower fasting glucose, and lower odds of type 2 diabetes. rs373863828 is common in Pacific Island populations (minor allele frequency (MAF) 0.096-0.

Association of diet quality, physical activity, and abdominal obesity with metabolic syndrome z-score in black and white adolescents in the US.

Background And Aims: Metabolic syndrome (MetS) affects ∼10% of adolescents and is associated with cardiometabolic disease risk. The most prevalent MetS component is abdominal obesity. Healthy diet and physical activity (PA) are inversely associated with abdominal obesity and may reduce MetS risk in youth.

Genome-wide association studies in Samoans give insight into the genetic architecture of fasting serum lipid levels.

The current understanding of the genetic architecture of lipids has largely come from genome-wide association studies (GWAS). To date, few GWAS have examined the genetic architecture of lipids in Polynesians, and none have in Samoans, whose unique population history, including many population bottlenecks, may provide insight into the biological foundations of variation in lipid levels. Here we performed a GWAS of four fasting serum lipid levels: total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TG) in a sample of 2849 Samoans, with validation genotyping for associations in a replication cohort comprising 1798 Samoans and American Samoans.

Exploring the Paradoxical Relationship of a Creb 3 Regulatory Factor Missense Variant With Body Mass Index and Diabetes Among Samoans: Protocol for the Soifua Manuia (Good Health) Observational Cohort Study.

Background: The prevalence of obesity and diabetes in Samoa, like many other Pacific Island nations, has reached epidemic proportions. Although the etiology of these conditions can be largely attributed to the rapidly changing economic and nutritional environment, a recently identified genetic variant, rs373863828 (CREB 3 regulatory factor, CREBRF: c.1370G>A p.

Evolutionary history of modern Samoans.

Archaeological studies estimate the initial settlement of Samoa at 2,750 to 2,880 y ago and identify only limited settlement and human modification to the landscape until about 1,000 to 1,500 y ago. At this point, a complex history of migration is thought to have begun with the arrival of people sharing ancestry with Near Oceanic groups (i.e.

A missense variant in CREBRF is associated with taller stature in Samoans.

Objectives: Studies have demonstrated that rs373863828, a missense variant in CREBRF, is associated with a number of anthropometric traits including body mass index (BMI), obesity, percent body fat, hip circumference, and abdominal circumference. Given the biological relationship between height and adiposity, we hypothesized that the effect of this variant on BMI might be due in part to an association of this variant with height.

Methods: We tested the hypothesis that minor allele of rs373863828 is associated with height in a Samoan population in two adult cohorts and in a separate cohort of children (age 5-18 years old) using linear mixed modeling.

Comprehensive mapping of the methylation landscape of 16 CpG-dense regions in oral and pharyngeal squamous cell carcinoma.

The goal of this study was to comprehensively interrogate and map DNA methylation across 16 CpG-dense regions previously associated with oral and pharyngeal squamous cell carcinoma (OPSCC). Targeted multiplex bisulfite amplicon sequencing was performed on four OPSCC cell lines and primary non-neoplastic oral epithelial cells. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed for a subset of associated genes.

Association of perfluoroalkyl substances exposure with cardiometabolic traits in an island population of the eastern Adriatic coast of Croatia.

Background: Exposure to perfluoroalkyl substances (PFAS), ubiquitous environmental contaminants, may be related to cardiometabolic diseases in adults. Studies in European populations to examine the association of PFAS exposure and comprehensive cardiometabolic traits and metabolic syndrome (MetS) are limited.

Methods: In this pilot cross-sectional study of a well-characterized adult population of the island of Hvar, situated off the eastern Adriatic coast of Croatia, we measured PFAS concentrations in plasma samples collected during 2007-2008 and examined their cross-sectional associations with cardiometabolic traits and MetS after adjustment of covariates (n = 122).