Protocol for improving equity in quantitative big data cleaning: lessons from longitudinal analysis of electronic health records from underrepresented and marginalized communities.

Background: Large biomedical datasets, including electronic health records (EHRs), are a significant source of epidemiologic data. To prepare an EHR for analysis, there are several data-cleaning approaches; here, we focus on data filtering. Common data-filtering methods employ rules that rely on data from socially constructed dominant populations but are inappropriate for marginalized populations, leading to the loss of valuable data and neglect of underrepresented communities.

Diet quality is positively associated with intake of traditional foods and does not differ by season in remote Yup'ik communities.

This study evaluated whether traditional food intake and diet quality differed by season in Yup'ik communities and examined the relationship between intake of traditional food groups and diet quality. Data were collected from 38 participants, ages 14-79 years, from two Yup'ik communities in Southwest Alaska from 2008 to 2010. Self-reported intake (24-h recalls) and dietary biomarker (nitrogen stable isotope ratio) data were collected twice in distinct seasons.

Obesity-Associated Dyslipidemia Is Moderated by Habitual Intake of Marine-Derived n-3 Polyunsaturated Fatty Acids in Yup'ik Alaska Native People: A Cross-Sectional Mediation-Moderation Analysis.

Background: Obesity leads to insulin resistance, altered lipoprotein metabolism, dyslipidemia, and cardiovascular disease. The relationship between long-term intake of n-3 polyunsaturated fatty acids (n-3 PUFAs) and prevention of cardiometabolic disease remains unresolved.

Objectives: The aim of this study was to explore direct and indirect pathways between adiposity and dyslipidemia, and the degree to which n-3 PUFAs moderate adiposity-induced dyslipidemia in a population with highly variable n-3 PUFA intake from marine foods.

Culturally adapting an evidence-based intervention to promote a healthy diet and lifestyle for Yup'ik Alaska native communities.

Underserved populations are at increased risk for obesity and related cardiovascular disease, type 2 diabetes, and other chronic diseases. Lack of access to healthy foods, sedentary behaviour, and other social environmental factors contribute to disease risk. Yup'ik Alaska Native communities are experiencing lifestyle changes that are likely to affect their cardiometabolic risks.

Efficacy of Air Filtration and Education Interventions on Indoor Fine Particulate Matter and Child Lower Respiratory Tract Infections among Rural U.S. Homes Heated with Wood Stoves: Results from the KidsAIR Randomized Trial.

Background: Millions of rural U.S. households are heated with wood stoves.

Tribal Deliberations about Precision Medicine Research: Addressing Diversity and Inequity in Democratic Deliberation Design and Evaluation.

Deliberative democratic engagement is used around the globe to gather informed public input on contentious collective questions. Yet, rarely has it been used to convene individuals exclusively from Indigenous communities. The relative novelty of using this approach to engage tribal communities and concerns about diversity and inequities raise important methodological questions.

Precision medicine research with American Indian and Alaska Native communities: Results of a deliberative engagement with tribal leaders.

Purpose: Amid calls for greater diversity in precision medicine research, the perspectives of Indigenous people have been underexplored. Our goals were to understand tribal leaders' views regarding the potential benefits and risks of such research, explore its priority for their communities, and identify the policies and safeguards they consider essential. This article reports on the participants' perspectives regarding governance and policy, stewardship and sharing of information and biospecimens, and informed consent.

Habitual Intake of Marine-Derived n-3 PUFAs is Inversely Associated with a Cardiometabolic Inflammatory Profile in Yup'ik Alaska Native People.

Background: The relationship between dietary n-3 PUFAs and the prevention of cardiometabolic diseases, including type 2 diabetes, is unresolved. Examination of the association between n-3 PUFAs and chronic low-grade inflammation in a population where many individuals have had an extremely high intake of marine mammals and fish throughout their lifespan may provide important clues regarding the impact of n-3 PUFAs on health.

Objectives: The aim of this study was to explore associations between concentrations of n-3 PUFAs resulting from habitual intake of natural food sources high in fish and marine mammals with immune biomarkers of metabolic inflammation and parameters of glucose regulation.

Seasonal variation in added sugar or sugar sweetened beverage intake in Alaska native communities: an exploratory study.

Excess added sugar intake contributes to tooth decay risk in Alaska Native communities. The goal of this exploratory study was to determine if there is seasonal variation in total added sugar intake or in the leading sources of added sugars in a Yup'ik population. Data were collected in spring and winter from 2008-2010 using self-reported intake data measured by 24-hour recall and by hair biomarker (carbon and nitrogen stable isotope).

In Vivo Functional Effects of a Novel and Common Variant in the Yup'ik Alaska Native Population.

Alaska Native people are under-represented in genetic research but have unique gene variation that may critically impact their response to pharmacotherapy. Full resequencing of in a cross-section of this population identified () a novel, relatively common single nucleotide polymorphism hypothesized to confer CYP2C9 poor metabolizer phenotype by disrupting the start codon. is present at a minor allele frequency of 6.

Indoor fine particulate matter and demographic, household, and wood stove characteristics among rural US homes heated with wood fuel.

Household heating using wood stoves is common practice in many rural areas of the United States (US) and can lead to elevated concentrations of indoor fine particulate matter (PM ). We collected 6-day measures of indoor PM during the winter and evaluated household and stove-use characteristics in homes at three rural and diverse study sites. The median indoor PM concentration across all homes was 19 µg/m , with higher concentrations in Alaska (median = 30, minimum = 4, maximum = 200, n = 10) and Navajo Nation homes (median = 29, minimum = 3, maximum = 105, n = 23) compared with Montana homes (median = 16, minimum = 2, maximum = 139, n = 59).

Characterization of CYP3A pharmacogenetic variation in American Indian and Alaska Native communities, targeting CYP3A4*1G allele function.

The frequencies of genetic variants in the CYP3A4 and CYP3A5 genes differ greatly across global populations, leading to profound differences in the metabolic activity of these enzymes and resulting drug metabolism rates, with important consequences for therapeutic safety and efficacy. Yet, the impact of genetic variants on enzyme activity are incompletely described, particularly in American Indian and Alaska Native (AIAN) populations. To characterize genetic variation in CYP3A4 and CYP3A5 and its effect on enzyme activity, we partnered with AIAN people living in two regions of Alaska: Yup'ik Alaska Native people living in the Yukon-Kuskokwim Delta region of rural southwest Alaska and AIAN people receiving care at the Southcentral Foundation in Anchorage, Alaska.

The derived allele of a novel intergenic variant at chromosome 11 associates with lower body mass index and a favorable metabolic phenotype in Greenlanders.

The genetic architecture of the small and isolated Greenlandic population is advantageous for identification of novel genetic variants associated with cardio-metabolic traits. We aimed to identify genetic loci associated with body mass index (BMI), to expand the knowledge of the genetic and biological mechanisms underlying obesity. Stage 1 BMI-association analyses were performed in 4,626 Greenlanders.

Wood stove interventions and child respiratory infections in rural communities: KidsAir rationale and methods.

Background: Acute lower respiratory tract infections (LRTIs) account for >27% of all hospitalizations among US children under five years of age. Residential burning of biomass for heat leads to elevated indoor levels of fine particulate matter (PM) that often exceed current health based air quality standards. This is concerning as PM exposure is associated with many adverse health outcomes, including a greater than three-fold increased risk of LRTIs.

The Nitrogen Isotope Ratio Is a Biomarker of Yup'ik Traditional Food Intake and Reflects Dietary Seasonality in Segmental Hair Analyses.

Background: The nitrogen isotope ratio (NIR) is a promising index of traditional food intake for an Alaska Native (Yup'ik) population, which can be measured in blood and hair. However, the NIR has not been calibrated to high-quality measures of Yup'ik traditional food intake.

Objectives: Our primary objective was to examine associations between intakes of Yup'ik traditional food groups, including fish, marine mammals, birds, land mammals, berries, greens, and total traditional foods, and the NIR.

Age of initiation of cigarette smoking and smokeless tobacco use among western Alaska Native people: Secondary analysis of the WATCH study.

Objective: This study examined self-reported age of tobacco initiation (cigarette smoking and smokeless tobacco [ST] use) and explored potential sex and generational group influences on tobacco use onset among Alaska Native (AN) adult ever tobacco users.

Methods: Secondary analysis of consolidated data from the Western Alaska Tribal Collaborative for Health (WATCH) study comprised 2800 AN adult ever tobacco users (1490 women, 1310 men; mean age = 39.2 years) from two rural western Alaska regions.

Identification of novel high-impact recessively inherited type 2 diabetes risk variants in the Greenlandic population.

Aims/hypothesis: In a recent study using a standard additive genetic model, we identified a TBC1D4 loss-of-function variant with a large recessive impact on risk of type 2 diabetes in Greenlanders. The aim of the current study was to identify additional genetic variation underlying type 2 diabetes using a recessive genetic model, thereby increasing the power to detect variants with recessive effects.

Methods: We investigated three cohorts of Greenlanders (B99, n = 1401; IHIT, n = 3115; and BBH, n = 547), which were genotyped using Illumina MetaboChip.

High tobacco use prevalence with significant regional and sex differences in smokeless tobacco use among Western Alaska Native people: the WATCH study.

Tobacco use prevalence among Alaska Native (AN) people living in Alaska is greater than the general population prevalence statewide and nationally. Better understanding of regional tobacco use is needed to improve cessation efforts and reduce prevalence. Using self-reported baseline data from the Western Alaska Tribal Collaborative for Health study, we describe tobacco use patterns among AN people in two western Alaska regions.

Dietary Vitamin K and Association with Hepatic Vitamin K Status in a Yup'ik Study Population from Southwestern Alaska.

Scope: The relationship between dietary vitamin K and plasma PIVKA-II concentration, a biomarker of hepatic vitamin K status, in a Yup'ik study population in southwestern Alaska is investigated.

Methods And Results: A total of 659 male and female, self-reported Yup'ik people, ≥14 years of age, were enrolled. Blood is collected for genotyping and plasma PIVKA-II biomarker analysis.

Bi-cultural dynamics for risk and protective factors for cardiometabolic health in an Alaska Native (Yup'ik) population.

Alaska Native people experience disparities in mortality from heart disease and stroke. This work attempts to better understand the relationships between socioeconomic, behavioral, and cardiometabolic risk factors among Yup'ik people of southwestern Alaska, with a focus on the role of the socioeconomic, and cultural components. Using a cross-sectional sample of 486 Yup'ik adults, we fitted a Partial Least Squares Path Model (PLS-PM) to assess the associations between components, including demographic factors [age and gender], socioeconomic factors [education, economic status, Yup'ik culture, and Western culture], behavioral factors [diet, cigarette smoking and smokeless tobacco use, and physical activity], and cardiometabolic risk factors [adiposity, triglyceride-HDL and LDL lipids, glycemia, and blood pressure].

Dietary and genetic influences on hemostasis in a Yup'ik Alaska Native population.

Fish and marine animals are important components of the subsistence diet of Alaska Native people, resulting in a high ω3 PUFA intake. The historical record for circumpolar populations highlights a tendency for facile bleeding, possibly related to ω3 PUFA effects on platelet activation and/or vitamin K-dependent clotting factors. To evaluate these two scenarios in Yup'ik people of southwestern Alaska, we examined the association between dietary ω3 PUFA intake and activities of clotting factor II, V, fibrinogen, PT, INR, PTT, and sP-selectin in 733 study participants, using the nitrogen isotope ratio of red blood cells as a biomarker of ω3 PUFA consumption.

Association between iq'mik smokeless tobacco use and cardiometabolic risk profile among Yup'ik Alaska Native people.

Objective: The traditional lifestyle of Yup'ik Alaska Native people, including a diet abundant in marine-based foods and physical activity, may be cardio-protective. However, iq'mik, a traditional form of smokeless tobacco used by >50% of Yup'ik adults, could increase cardiometabolic (CM) risk. Our objective was to characterize the associations between iq'mik use and biomarkers of CM status (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], systolic blood pressure [SBP] and diastolic blood pressure [DBP], glycated hemoglobin [HbA1c], fasting blood glucose [FBG], waist circumference [WC], and body mass index [BMI]).

Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people.

Background: Vitamin D deficiency is a well-documented public health issue with both genetic and environmental determinants. Populations living at far northern latitudes are vulnerable to vitamin D deficiency and its health sequelae, although consumption of traditional native dietary pattern rich in fish and marine mammals may buffer the effects of reduced sunlight exposure. To date, few studies have investigated the genetics of vitamin D metabolism in circumpolar populations or considered genediet interactions with fish and n-3 fatty acid intake.

Polymorphisms in stearoyl coa desaturase and sterol regulatory element binding protein interact with N-3 polyunsaturated fatty acid intake to modify associations with anthropometric variables and metabolic phenotypes in Yup'ik people.

Scope: n-3 polyunsaturated fatty acid (n-3 PUFA) intake is associated with protection from obesity; however, the mechanisms of protection remain poorly characterized. The stearoyl CoA desaturase (SCD), insulin-sensitive glucose transporter (SLC2A4), and sterol regulatory element binding protein (SREBF1) genes are transcriptionally regulated by n-3 PUFA intake and harbor polymorphisms associated with obesity. The present study investigated how consumption of n-3 PUFA modifies associations between SCD, SLC2A4, and SREBF1 polymorphisms and anthropometric variables and metabolic phenotypes.