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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.

Food sovereignty among Inuit in Nunavut, Canada has long meant year-round harvest of country (hunted, fished, or gathered) food. In recent decades, climatic and non-climatic challenges have complicated these subsistence activities, threatening food security. We examine the meaning of country food, identify determinants of low-yield periods of country food harvest and their effects on community health, and summarize coping strategies and ideas for sustaining food security during these “leaner” periods. Thirty semi-structured interviews were conducted in July and August of 2018 with elders and/or hunters and trappers in Cambridge Bay and Pond Inlet. We found country food holds diverse meanings in the lives of our participants, including for their diet and nutrition, health, Inuit identity and traditions, practice of harvest and subsistence, and spirituality. Participants reported reduced wildlife populations, environmental or weather issues, changing wildlife migration patterns, and financial or equipment-related constraints as determinants of low-yield periods of harvest. Community health is impacted during lean periods across four interrelated dimensions: “craving” of country food, physical health, mental health, and nutrition. Due to their lifelong reliance on country food, elders were described as being particularly vulnerable and are prioritized within the traditional food sharing system. The most commonly cited coping strategies were turning to intra- or inter-community food sharing networks for country food and purchasing groceries. To support communities during low-yield periods of harvest, participants suggested increased support for Hunters and Trappers Organizations to acquire country food for community distribution, as well as greater financial and equipment support for harvesters.

BACKGROUND/OBJECTIVES: In Samoa, where 80% of the adult population is living with obesity, understanding the determinants of adiposity and growth during infancy may inform prevention efforts. We examined the association of a missense variant, rs373863828, in the CREBRF gene with body composition in Samoan infants. Adults with one or more copies of the rs373863828 minor allele (A) have higher odds of obesity, based on body-mass index (BMI), but paradoxically decreased odds of diabetes compared to those without the allele. Our study may offer novel insight into the natural history and pathogenesis of this unexpected relationship. SUBJECTS/METHODS: In a prospective study, we measured body composition in early infancy, and at 2- and 4-months of age using anthropometry and Dual-Energy X-Ray Absorptiometry (DXA). We genotyped subjects at the CREBRF rs373863828 locus and compared infants with (AA/AG) and without (GG) the variant. In longitudinal analyses, we calculated the absolute change in each outcome from the early infant to the 4-month assessment, adjusting for baseline and other covariates. RESULTS: In cross-sectional analyses, there was no significant difference in infant BMI or fat mass by genotype. After adjusting for covariates, infants with the variant had 4.0 ± 1.8g more bone mass (p=0.026) and 210.9 ±79.6g more lean mass (p=0.009) at 4-months and accumulated 176.9 ± 73.0g more lean mass between the early infant and 4-month assessment (p=0.017). CONCLUSIONS: The CREBRF rs373863828 minor allele (A) was not associated with increased BMI or adiposity in Samoan infants, but instead with increased lean and bone mass. Our findings suggest that lean (i.e. muscle) and bone mass accretion should be explored as pathways to explain the ‘protective’ effect of the CREBRF variant against diabetes.

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. We identified multiple genome-wide significant associations (P < 5 × 10(−8)) previously seen in other populations—APOA1 with TG, CETP with HDL, and APOE with TC and LDL—and several suggestive associations (P < 1 × 10(−5)), including an association of variants downstream of MGAT1 and RAB21 with HDL. However, we observed different association signals for variants near APOE than what has been previously reported in non-Polynesian populations. The association with several known lipid loci combined with the newly identified associations with variants near MGAT1 and RAB21 suggest that while some of the genetic architecture of lipids is shared between Samoans and other populations, part of the genetic architecture may be Polynesian-specific.

Pacific Islanders face many health disparities, including higher rates of cardiovascular disease, cancer, obesity, and diabetes compared to other racial and ethnic groups. Specifically, the Marshallese population suffers disproportionately from type 2 diabetes, with rates 400% higher than the general US population. As part of an ongoing community-based participatory research (CBPR) partnership, 148 participants were recruited for a study examining genetic variants to better understand diabetes. Participants provided a saliva specimen in an Oragene® DNA self-collection kit. Each participant provided approximately 2 mL volume of saliva and was asked qualitative questions about their experience. The study yielded a recruitment rate of 95.5%. Among the 148 persons who participated, 143 (96.6%) agreed to be contacted for future studies; 142 (95.9%) agreed to have their samples used for future IRB-approved studies; and 144 (97.3%) gave permission for the researchers to link information from this study to other studies in which they had participated. Qualitative responses showed that the majority of participants were willing to participate because of their desire to contribute to the health of their community and to understand the genetic influence related to diabetes. This study demonstrates willingness to participate in genetic research among Marshallese living in Arkansas. Willingness was likely enhanced because the feasibility study was part of a larger CBPR effort. This study is important to community stakeholders who have voiced a desire to collaboratively conduct genetic research related to diabetes, perinatal outcomes, and cancer.

This review describes some of the unique challenges faced by the US-Affiliated Pacific Islands (USAPIs) in addressing diabetes prevention and care and presents innovative population-level strategies that have been employed to address them. Challenges include an unhealthy food environment and a strained health care infrastructure, both compounded by geography. Innovations in addressing these challenges include attempts to modify the food environment, a focus on early life prevention, and task shifting among the health workforce. Many of the successful interventions share a focus on culture, community, and capacity building. Although the USAPIs are uniquely challenged by environmental, structural, and health system barriers, there have been a number of innovative and successful strategies employed that highlight the resilience of these island nations in addressing their current disease burden when provided with the opportunity and resources to do so. Health policies to protect, support, and promote diabetes prevention and care are essential and may be informed by the interventions described.

Samoans are a unique founder population with a high prevalence of obesity, making them well suited for identifying new genetic contributors to obesity. We conducted a genome-wide association study (GWAS) in 3,072 Samoans, discovered a variant, rs12513649, strongly associated with body mass index (BMI) (P = 5.3 × 10(-14)), and replicated the association in 2,102 additional Samoans (P = 1.2 × 10(-9)). Targeted sequencing identified a strongly associated missense variant, rs373863828 (p.Arg457Gln), in CREBRF (meta P = 1.4 × 10(-20)). Although this variant is extremely rare in other populations, it is common in Samoans (frequency of 0.259), with an effect size much larger than that of any other known common BMI risk variant (1.36-1.45 kg/m(2) per copy of the risk-associated allele). In comparison to wild-type CREBRF, the Arg457Gln variant when overexpressed selectively decreased energy use and increased fat storage in an adipocyte cell model. These data, in combination with evidence of positive selection of the allele encoding p.Arg457Gln, support a 'thrifty' variant hypothesis as a factor in human obesity.

Background Organophospate flame retardants (PFRs) are chemicals of emerging concern due to restrictions on polybrominated diphenyl ether flame retardant formulations. We describe the occurrence, variability, and predictors of urinary metabolites of PFRs among pregnant women. Methods In 2014–2015, 59 women from Providence, RI provided up to 3 spot urine samples during pregnancy (~12, 28, and 35 weeks’ gestation). We created a pooled urine sample per woman and measured nine relevant metabolites in individual and pooled samples. We used linear mixed models to calculate intraclass correlation coefficients (ICCs) across the 3 measurements and to assess sociodemographic and dietary predictors of PFRs. Results The median (IQR) of bis-2-chloroethyl phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), and diphenyl phosphate (DPhP), the metabolites most frequently detected, from pooled samples were: 0.31 μg/L (0.17–0.54), 1.18 μg/L (0.64–2.19), 0.93 μg/L (0.72–1.97), respectively. We observed fair to good reproducibility for BCEP (ICC = 0.50), BDCPP (ICC = 0.60), and DPhP (ICC = 0.43), and excellent agreement between the urinary flame retardant metabolite concentrations averaged across pregnancy versus pooled urine sample concentrations for BCEP (ICC = 0.95), BDCPP (ICC = 0.89), and DPhP (ICC = 0.93). Adjusting for pertinent sociodemographic factors and gestational week of urine collection, each 1 kg increase in pre-pregnancy weight was associated with greater BCEP (1.1%; 95% CI: 0.1, 2.1), BDCPP (1.5%; 95% CI: 0.3, 2.7), and DPhP (0.5%; 95% CI: 0.0, 1.1). Dietary factors were generally not associated with urinary flame retardant metabolites. Conclusions Urinary concentrations of BCEP, BDCPP, and DPhP were frequently detected among women in this pilot study and had fair reproducibility across pregnancy. Body size may be an important predictor of urinary flame retardant metabolite concentrations. Electronic supplementary material The online version of this article (doi:10.1186/s12940-017-0247-z) contains supplementary material, which is available to authorized users.

The objective of this study is to describe the utilization of prenatal care in American Samoan women and to identify socio-demographic predictors of inadequate prenatal care utilization. Using data from prenatal clinic records, women (n = 692) were categorized according to the adequacy of prenatal care utilization index as having received adequate plus, adequate, intermediate or inadequate prenatal care during their pregnancy. Categorical socio-demographic predictors of the timing of initiation of prenatal care (week of gestation) and the adequacy of received services were identified using one way analysis of variance and independent samples t tests. Between 2001 and 2008 85.4 % of women received inadequate prenatal care. Parity (P = 0.02), maternal unemployment (P = 0.03), and both parents being unemployed (P = 0.03) were negatively associated with the timing of prenatal care initiation. Giving birth in 2007–2008, after a prenatal care incentive scheme had been introduced in the major hospital, was associated with earlier initiation of prenatal care (20.75 vs. 25.12 weeks; P < 0.01) and improved adequacy of received services (95.04 vs. 83.8 %; P = 0.02). The poor prenatal care utilization in American Samoa is a major concern. Improving healthcare accessibility will be key in encouraging women to attend prenatal care. The significant improvements in the adequacy of prenatal care seen in 2007–2008 suggest that the prenatal care incentive program implemented in 2006 may be a very positive step toward addressing issues of prenatal care utilization in this population.

Non-communicable diseases (NCDs) now account for more than 36 million deaths each year; many of which are premature. Pacific Islanders are some of the worst afflicted by obesity and diabetes with prevalence of both diseases rising disproportionately faster in the Pacific region over the past three decades than in the rest of the world. A high burden of disease is also found among enclaves of Pacifican migrants in the USA, Australia, and New Zealand. Urgent action is needed to alleviate the high economic and personal costs now associated with NCDs in Pacific Islanders. In this article, we describe contributors to the temporal trends in obesity and diabetes, discuss the current burden of disease in the Pacific Islands and among migrant communities, and suggest priorities for future research in this area. Finally, we discuss challenges unique to intervention among Pacific Islanders and highlight promising opportunities to reduce the NCD burden.

Background As obesity has increased worldwide, so have levels of obesity during pregnancy and excess gestational weight gain (GWG). The aim of this paper was to describe GWG among American Samoan women and examine the association between GWG and four adverse pregnancy and infant outcomes: cesarean delivery, small- and large-for-gestational age (SGA/LGA), and infant overweight/obesity. Methods Data were extracted from prenatal care records of 632 Samoan women. Mixed-effects growth models were used to produce individual weight-for-gestational week curves from which second and third trimester weight gain was estimated. Binary logistic regression was used to examine associations between GWG and the outcomes of interest. Results Most women were overweight/obese in early pregnancy (86%) and 78% exceeded the Institute of Medicine GWG guidelines. Greater GWG in the second trimester and early pregnancy weight were independently associated with increased odds of a c-section (OR 1.40 [95% CI: 1.08, 1.83]) and OR 1.51 [95% CI: 1.17, 1.95], respectively). Risk of delivering a LGA infant increased with greater third trimester weight gain and higher early pregnancy weight, while second trimester weight gain was negatively associated with SGA. Risk of infant overweight/obesity at 12 months increased with early pregnancy weight (OR: 1.23 [95% CI: 1.01, 1.51]) and infant birthweight. Conclusions The high levels of pregnancy obesity and excessive GWG in American Samoa suggest that it is important for physicians to encourage women into prenatal care early and begin education about appropriate GWG and the potential risks of excess weight gain for both the mother and baby.