Objective:To identify patterns of gestational weight gain (pGWG) trajectories in the first 20 weeks of gestation and to determine the association of these patterns with the delivery of large-for-gestational-age (LGA) infants among women with insulin-dependent diabetes mellitus (IDDM). Study design:Analysis of data collected prospectively in a Diabetes in Pregnancy Program Project Grant 7/1978 to 6/1993. Sparse functional principal components analysis was used to identify clusters defining phenotypes of women with similar pGWG in the first 20 weeks of gestation. Generalized estimating equations (GEEs) were used to estimate the association between maternal phenotype according to pGWG and odds of LGA (> 90th percentile) at birth, adjusting for predefined covariates and confounders; age, age of diagnosis of diabetes, race, parity, chronic hypertension, nephropathy, retinopathy, body mass index (BMI), and glycohemoglobin A1. GEEs were also used to examine the association of LGA and total weight gain over the first 20 weeks of gestation. Results:A total of 349 pregnancies were included in this analysis. Three phenotypes of pGWG were identified and classified as high pGWG (highest 25% of trajectories; n = 84), moderate pGWG (middle 50% of trajectories; n = 176), and low pGWG (lowest 25% of trajectories; n = 89). Phenotype was positively associated with prepregnancy BMI (p < 0.0001) and total GWG (p < 0.0001). Women with high pGWG (adjusted odds ratio [aOR] = 3.54; 95% confidence interval [CI], 1.31-9.51) and moderate pGWG (aOR = 2.41; 95% CI, 1.09-5.35) had significantly increased odds of delivering an LGA infant, compared to women in the low pGWG. However, total weight gain over the first 20 weeks of gestation was not significantly associated with delivery of an LGA infant. Conclusions:Moderate or high pGWG during the first 20 weeks of gestation was associated with increased odds of delivering an LGA infant. Future studies should consider pGWG in early pregnancy rather than overall early GWG to strategize interventions when examining the likelihood of delivering an LGA infant.

Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood (n = 6454) and lung (n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank-derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.

Structural variants (SVs) are often excluded from genetic research because they are difficult to call, but they can have substantial effects on phenotypic traits. SVs have not previously been characterized in Samoans, an understudied population with a high burden of complex diseases. Using short-read whole genome sequencing data, we called SVs in 1,276 Samoans and created a Samoan-specific imputation panel inclusive of both SVs and single nucleotide variants (SNVs), called the Soifua Manuia-SV panel. Using this panel, we imputed SVs and SNVs in 3,611 Samoans with array data, enabling analysis of SV-phenotype associations in a sample of 4,887 Samoan participants. We evaluated imputation performance in Samoans against two other reference panels: (i) an SNV-only Samoan-specific reference panel, to assess whether SV inclusion impacts SNV imputation, and (ii) an SV and SNV, multi-ancestry reference panel composed of 1000 Genomes participants, which did not include Polynesians, to assess the importance of including the target population in the reference panel. The Soifua Manuia-SV panel substantially outperformed the multi-ancestry SV and SNV panel, yielding 5.5 million more high-quality (r2 ≥ 0.8) variants, including over 8,000 more high-quality SVs. SNV imputation based on the two Samoan-specific panels performed similarly overall, suggesting that SV inclusion does not strongly impact SNV imputation quality. This work highlights the importance of population representation for accurate imputation.

Dyslipidemia is a significant risk factor for cardiovascular disease (CVD), the leading cause of death in Samoa. 1 Polygenic scores (PGS) for lipid traits offer promise for improved CVD risk prediction, 4,5 yet their performance in Pacific Islander populations - comprising only 0.002% of GWAS participants as of 2024 3 - remains unknown. We evaluated the transferability of multi-ancestry PGS for LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglycerides (TG), and total cholesterol (TC) in 4,342 Samoan adults across five cohorts spanning 1990-2010. PGS from Graham et al. 8 and Kanoni et al. 9 multi-ancestry meta-analyses were harmonized with genome-wide imputed genotypes using a Samoan-specific reference panel 21 and performance was assessed via incremental R² from linear mixed models with bootstrapped confidence intervals. 25 HDL-C showed the highest performance (incremental R² 5.0-15.0%), followed by TC (5.0-10.7%), LDL-C (5.7-8.6%), and TG (3.5-7.0%). Critically, meaningful LDL-C performance was achieved only with the genome-wide PRS-CS score (99.6-99.7% variant matching), while a curated pruning-and-thresholding score achieved ∼9% matching and near-zero performance. These findings establish the first systematic lipid PGS benchmarks in Samoans, demonstrating meaningful transferability when genome-wide variant coverage is ensured, and highlight variant harmonization as a critical precondition for PGS deployment in underrepresented populations.

Dyslipidemia is a significant risk factor for cardiovascular disease (CVD), the leading cause of death in Samoa. Polygenic scores (PGS) for lipid traits offer promise for improved CVD risk prediction; however, their performance in Pacific Islander populations - comprising only 0.002% of GWAS participants as of 2024 - remains unknown. We evaluated the transferability of multi-ancestry PGS for LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglycerides (TG), and total cholesterol (TC) in 4,342 Samoan adults across five cohorts spanning 1990-2010. PGS from Graham et al. and Kanoni et al. multi-ancestry meta-analyses were harmonized with genome-wide imputed genotypes using a Samoan-specific reference panel, and performance was assessed via incremental R2 from linear mixed models with bootstrapped confidence intervals. HDL-C showed the highest performance (incremental R2 5.0-15.0%), followed by TC (5.0-10.7%), LDL-C (5.7-8.6%), and TG (3.5-7.0%). Critically, meaningful LDL-C performance was achieved only with the genome-wide PRS-CS score (99.6-99.7% variant matching), while a curated pruning-and-thresholding score achieved ∼9% matching and near-zero performance. These findings establish systematic lipid PGS benchmarks in Samoans, demonstrating meaningful transferability when genome-wide variant coverage is ensured, and highlight variant harmonization as a critical precondition for PGS deployment in underrepresented populations.

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. We compared this panel to 1000G and TOPMed panels based on imputed variants using genotyping array data for 1,834 Samoan participants who were not part of the panels. The 1000G + 1285 Samoan panel yielded up to 2.25-2.76 times more well-imputed (r 2 ≥ 0.80) variants than TOPMed and 1000G. There was improved imputation accuracy across the minor allele frequency (MAF) spectrum, although it was more pronounced for variants with 0.01 ≤ MAF ≤ 0.05. Imputation accuracy (r 2 ) was greater for population-specific variants (high fixation index, F ST ) and those from larger haplotypes (high LD score). The gain in imputation accuracy over TOPMed was largest for small haplotypes (low LD score), reflecting the Samoan panel's ability to capture population-specific variation not well tagged by other panels. We also augmented the 1000G reference panel with varying numbers of Samoan samples and found that panels with 48 or more Samoans included outperformed TOPMed for all variants with MAF ≥ 0.001. This study identifies variants with improved imputation using population-specific reference panels and provides a framework for constructing other population-specific reference panels.

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. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction.

ABSTRACTCurrent 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.652C>T, p.R218*; posterior probability = 0.9987) inBTNL9and both lower HDL-C and greater triglycerides (TG). Meta-analysis across this and several other cohorts of Polynesian ancestry from Samoa, American Samoa, and Aotearoa New Zealand confirmed the presence of this association (βHDL-C= -1.60 mg/dL,pHDL-C= 7.63 × 10−10; βTG= 12.00 mg/dL,pTG= 3.82 × 10−7). While this variant appears to be Polynesian-specific, there is also evidence of association from other multi-ancestry analyses in this region. This work provides evidence of a previously unexplored contributor to the genetic architecture of lipid levels and underscores the importance of genetic analyses in understudied populations.

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. We calculated z-scores using 2006 World Health Organization (WHO) child growth standards for the 4-week anthropometric measures (weight, length, and head circumference), the ponderal index, and weekly growth rates. We used multiple informant models to examine window-specific associations between individual OPE metabolites and anthropometric outcomes. We further modeled OPEs as a mixture for window-specific associations with 4-week anthropometric outcomes using mean field variational Bayesian inference procedure for lagged kernel machine regression (MFVB-LKMR). We stratified the models by infant sex. RESULTS:Diphenyl phosphate (DPHP) in mothers at 16 weeks, and bis(2-chloroethyl) phosphate (BCEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) at delivery were positively associated with z-scores of weight, length, and head circumference in all infants at 4 weeks of age. After stratifying by infant sex, positive associations were only observed in males for DPHP at 16 weeks and BCEP at delivery and in females for BDCIPP at delivery. Negative associations not present in all infants were observed in males for di-n-butyl phosphate (DNBP) at 26 weeks of gestation with weight z-score and DPHP at delivery with head circumference z-score. Results were generally similar using MFVB-LKMR models with more conservative 95 % credible intervals. We did not identify consistent associations of gestational OPE metabolite concentrations with the ponderal index and weekly growth rates. CONCLUSION:In this cohort, exposure to OPEs during gestation was associated with altered infant anthropometry at 4 weeks after birth.

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 CETP associate with serum lipid profiles and cardiovascular disease. Here, sequencing of CETP identified a missense variant rs1597000001 (p.Pro177Leu) specific to Māori and Pacific people that associates with higher HDL-C and lower LDL-C levels. Each copy of the minor allele associated with higher HDL-C by 0.236 mmol/L and lower LDL-C by 0.133 mmol/L. The rs1597000001 effect on HDL-C is comparable with CETP Mendelian loss-of-function mutations that result in CETP deficiency, consistent with our data, which shows that rs1597000001 lowers CETP activity by 27.9%. This study highlights the potential of population-specific genetic analyses for improving equity in genomics and health outcomes for population groups underrepresented in genomic studies.

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. We examined the associations of average maternal OPE metabolite concentrations with OPE metabolite concentrations in childhood, characterized childhood OPE trajectories with latent class growth analysis (LCGA), and examined factors related to trajectory membership. Results Bis(2-chloroethyl) phosphate (BCEP) had the lowest median concentrations over time (0.66–0.97 mg/L) while the median concentrations of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) increased with age (1.44–3.80 mg/L). The median concentrations of diphenyl phosphate (DPHP) fluctuated between 1.96 and 2.69 mg/L. Intraclass correlation coefficients for urinary metabolites measured at five time points indicated high variability within individuals (0.13–0.24). Average maternal urinary BCEP and BDCIPP were associated with concentrations in early childhood. Maternal education, the birth year of the child, and having a carpet in the main activity room were associated with BCEP and BDCIPP trajectory while none of the factors were associated with DPHP trajectory. Significance The trajectory analysis showed different patterns of urinary OPE metabolite concentrations, suggesting the need to collect multiple samples to adequately reflect OPE exposure. Impact statement In this well-established cohort, we evaluated the patterns of urinary OPE metabolites in children ages 1–8 years. The number of repeated measures over childhood has not been achieved in prior studies. Our results suggested the high variability of urinary OPE metabolites within individuals. Maternal metabolite concentrations during pregnancy were related to child concentrations at ages 1–3 years. BCEP, BDCIPP, and DPHP demonstrated different trajectories in children, which suggests that multiple samples may be required to capture OPE exposure patterns in childhood.

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. We did not observe statistically significant association within each separate Polynesian subgroup. Bayesian meta-analysis of the Aotearoa New Zealand Polynesian and Samoan samples resulted in a posterior mean effect size estimate of +0.21 kg/m2, with a 95% credible interval [+0.03 kg/m2, +0.39 kg/m2]. While the Bayes Factor (BF) of 0.77 weakly favors the null, the BF = 1.4 Bayesian support interval is [+0.04, +0.20]. These results suggest that rs9939609 in FTO may have a similar effect on mean BMI in people of Polynesian ancestries as previously observed in other ancestral groups.

Organophosphate esters (OPEs) are developmental toxicants in experimental studies of animals, but limited evidence is available in humans. We included 340 mother-infant pairs in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio, USA) for the analysis. We evaluated gestational exposure to OPEs with gestation age at birth and newborn anthropometric measures. We quantified four OPE urinary metabolites at 16 weeks and 26 weeks of gestation. We extracted gestational age at birth, newborn weight, length, and head circumference from the chart review. We calculated z-scores for these anthropometric measures and the ponderal index. We used multiple informant models to examine the associations between repeated OPE measurements and the outcomes. We used modified Poisson regression to estimate the association of gestational exposure to OPEs with preterm birth. We also explored effect modification by infant sex and the potential mediation effect by the highest maternal blood pressure and glucose levels. We found that bis(2-chloroethyl) phosphate (BCEP) at 16 weeks and diphenyl phosphate at 26 weeks of pregnancy were positively associated with gestational age and inversely associated with preterm birth. In female newborns, BCEP at 16 weeks was inversely related to birth weight and length z-scores. In male newborns, we observed negative associations of 26-week di-n-butyl phosphate with the ponderal index at birth. No mediation by the highest maternal blood pressure or glucose levels during pregnancy was identified. In this cohort, gestational exposure to some OPEs was associated with gestational age, preterm birth, and neonatal anthropometric measures. Certain associations tended to be window- and infant sex-specific.

ABSTRACT Background The Pacific-specific minor allele of rs373863828, a missense variant in CREB3 Regulatory Factor ( CREBRF ), is associated with several cardiometabolic phenotypes in Polynesian peoples, but the variant’s function remains poorly understood. To broaden our understanding of this variant, we used joint multivariate and network analyses to examine the relationships between rs373863828 and a panel of correlated anthropometric and lipid phenotypes. Methods We tested the association of rs373863828 with a panel of phenotypes (body mass index [BMI], weight, height, HDL cholesterol, triglycerides, and total cholesterol) under a multivariate Bayesian association model in a cohort from Samoa (N = 1 632), a Māori and Pacific Island (Polynesian) cohort from Aotearoa New Zealand (N = 1 419), and the combined cohort (N = 2 976). An expanded set of phenotypes (adding estimated fat and fat-free mass, abdominal circumference, hip circumference, and abdominal-hip ratio) was also tested in the Samoa cohort (N = 1 496). Bayesian networks were learned to further understand the structure of the relationships. Results In the Samoa cohort, significant associations (log 10 Bayes factor ≥5.0) were found between rs373863828 and the overall phenotype panel (7.97), weight (8.35) and BMI (6.39). In the Aotearoa New Zealand cohort, suggestive associations (log 10 Bayes factor between 1.5 and 5) were found between rs373863828 and the overall phenotype panel (3.64), weight (3.30), and BMI (1.79). In the combined cohort, concordant signals with stronger magnitudes were observed. In the expanded phenotype analyses among the Samoa cohort, significant associations were also observed between rs373863828 and fat mass (5.68), abdominal circumference (5.37), and hip circumference (5.15). Bayesian networks provided evidence for a direct association of rs373863828 with weight and indirect associations with height and BMI. Conclusions When correlation structures were considered, multivariate Bayesian analyses provided additional evidence of rs373863828’s pleiotropic effects and highlighted a strong direct effect only on weight.

Background: Metabolic syndrome (MetS) affects w10% of U.S. adolescents. Abdominal obesity is the most prevalent component and may indicate MetS risk in adolescents undergoing weight loss surgery.Objectives: Assess MetS risk/severity and its association with abdominal obesity (measured by sagittal abdominal diameter, SAD) before and after weight loss surgery in adolescents to determine whether SAD predicts MetS risk in this population.Setting: Data were collected in the Teen Longitudinal Assessment of Bariatric Surgery (TeenLABS) study at 5 sites (U.S. children's hospitals) performing weight-loss surgery in adolescents. The current study is a secondary analysis of these data.Methods: We examined data collected presurgery through 5 years postsurgery. MetS risk/severity was defined using the MetS severity z score (MetS-z), and MetS prevalence was determined using ageappropriate criteria. Association between SAD and MetS-z was evaluated with an adjusted linear mixed model.Results: Among 228 individuals (75% female, 72% White), mean age 16.5 years and body mass index (BMI) 53 kg/m2, 79% met MetS criteria pre-urgery. MetS-z (1.5) and SAD (32cm) were correlated (r = 0.6, P , .0001) presurgery, and both improved significantly at 6 months, 1, and 5 years postsurgery, remaining highly correlated at each timepoint. SAD predicted MetS-z (b = 0.118; 95% CI, 0.109, 0.127) after adjustment for age, visit, surgery type, and caregiver education.Conclusions: Abdominal obesity is a key MetS risk marker in youth undergoing weight loss surgery. Both SAD and Met-z measures may be useful for MetS risk assessment and tracking postsurgery changes in this population, but more research is needed to identify effective lifestyle interventions targeting abdominal obesity. (Surg Obes Relat Dis 2023;19:350-355.) (c) 2023 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

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.Glu386*). This allele encodes a truncated protein that is absent from the cell surface and is loss-of-function. The fibroblasts of the patients do not respond to type I IFNs (IFN-α2, IFN-ω, or IFN-β). Remarkably, this IFNAR1 variant has a minor allele frequency >1% in Samoa and is also observed in the Cook, Society, Marquesas, and Austral islands, as well as Fiji, whereas it is extremely rare or absent in the other populations tested, including those of the Pacific region. Inherited IFNAR1 deficiency should be considered in individuals of Polynesian ancestry with severe viral illnesses.

ABSTRACT Telomeres shorten in replicating somatic cells, and telomere length (TL) is associated with age-related diseases 1,2 . To date, 17 genome-wide association studies (GWAS) have identified 25 loci for leukocyte TL 3–19 , but were limited to European and Asian ancestry individuals and relied on laboratory assays of TL. In this study from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of TL in n=109,122 trans-ethnic (European, African, Asian and Hispanic/Latino) individuals. We identified 59 sentinel variants (p-value <5×10 −9 ) from 36 loci (20 novel, 13 replicated in external datasets). There was little evidence of effect heterogeneity across populations, and 10 loci had >1 independent signal. Fine-mapping at OBFC1 indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 ( STN1 ). We further identified two novel genes, DCLRE1B ( SNM1B ) and PARN , using a multi-variant gene-based approach.

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program (n = 63,302) and UK Biobank (n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.

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 43.8 years) and 2017-19. Results: Mean BMI increased from 32.1 to 33.5 kg/m(2) in males (n = 220, p = 1.3 x10(-8)) and from 35.9 to 37.8 kg/m(2) in females (n = 260, p = 1.2 x10(-13)). In females, the A allele was associated with a higher rate-of-change (0.150 kg/m(2)/year/allele, p = 1.7 x10(-4)). Across 10-year age groups, mean BMI rate-of-change was lower in older participants. The BMI rate of change differed by genotype: it was, in females with AA genotype, approximately half that seen in GG and AG participants. In females lower baseline household asset scores were associated with a higher rate-of-change (p = 0.002). Conclusions: In Samoans, the minor A allele of rs373863828 is associated with an increased rate-of-change in BMI in females. On average, BMI of females with the AA genotype increased 0.30 kg/m(2)/year more than of those with the GG genotype.

Background: 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. Materials & methods: 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. Associations between cardiometabolic traits and loci were assessed using linear models. Results: 22 CpG loci were significantly associated with systolic blood pressure. Twenty were stable and two were dynamic. Conclusion: Multiple genes may be involved in the determination of systolic blood pressure level via stable epigenetic programming, potentially established earlier in life.