Genetic variant rs1205 is associated with COVID-19 outcomes: The Strong Heart Study and Strong Heart Family Study.

BACKGROUND: Although COVID-19 infection has been associated with a number of clinical and environmental risk factors, host genetic variation has also been associated with the incidence and morbidity of infection. The CRP gene codes for a critical component of the innate immune system and CRP variants have been reported associated with infectious disease and vaccination outcomes. We investigated possible associations between COVID-19 outcome and a limited number of candidate gene variants including rs1205. METHODOLOGY/PRINCIPAL FINDINGS: The Strong Heart and Strong Heart Family studies have accumulated detailed genetic, cardiovascular risk and event data in geographically dispersed American Indian communities since 1988. Genotypic data and 91 COVID-19 adjudicated deaths or hospitalizations from 2/1/20 through 3/1/23 were identified among 3,780 participants in two subsets. Among 21 candidate variants including genes in the interferon response pathway, APOE, TMPRSS2, TLR3, the HLA complex and the ABO blood group, only rs1205, a 3' untranslated region variant in the CRP gene, showed nominally significant association in T-dominant model analyses (odds ratio 1.859, 95%CI 1.001-3.453, p = 0.049) after adjustment for age, sex, center, body mass index, and a history of cardiovascular disease. Within the younger subset, association with the rs1205 T-Dom genotype was stronger, both in the same adjusted logistic model and in the SOLAR analysis also adjusting for other genetic relatedness. CONCLUSION: A T-dominant genotype of rs1205 in the CRP gene is associated with COVID-19 death or hospitalization, even after adjustment for relevant clinical factors and potential participant relatedness. Additional study of other populations and genetic variants of this gene are warranted.

Return of Participants' Incidental Genetic Research Findings: Experience from a Case-Control Study of Asthma in an American Indian Community.

The proper communication of clinically actionable findings to participants of genetic research entails important ethical considerations, but has been challenging for a variety of reasons. We document an instance of the return of individual genetic results in the context of a very rural American Indian community, in hopes of providing insight to other investigators about potentially superior or inferior courses of action. This was a case/control study of asthma among 324 pediatric participants. Subsequently, microarray genotype data became available, providing over 2 million variants, incidentally including some conferring risk for conditions for which the American College of Medical Genetics recommends return of results. The study investigators engaged in extensive consultation with the IRB, the tribal government, and local clinicians to better inform our approach. We were able to notify the two participants heterozygous for the one clinically actionable variant identified. One participant welcomed this information and proceeded to obtain further clinical work-up; the other participant declined further follow-up. While demanding considerable time and effort, the return of clinically actionable genetic results is important from both an ethical perspective and to provide an improved trust relationship with the community of research participants.

Return of Participants' Incidental Genetic Research Findings: Experience from a Case-Control Study of Asthma in an American Indian Community.

PURPOSE: The proper communication of clinically actionable findings to participants of genetic research entails important ethical considerations, but has been challenging for a variety of reasons. We document an instance of return of individual genetic results in the context of a very rural American Indian community, in hopes of providing insight to other investigators about potentially superior or inferior courses of action. METHODS: The original study was a case/control study of asthma among 324 pediatric participants. The study utilized a genotyping microarray assessing over 2 million variants, including one conferring risk for hypertrophic cardiomyopathy for which the American College of Medical Genetics recommends return of results to participants. The study investigators engaged in extensive consultation with the IRB, the Tribal government and local clinicians to better inform our approach. RESULTS: With some difficulty we were able to notify the 2 participants heterozygous for this variant. One participant welcomed this information and proceeded to obtain further clinical work-up; the other participant declined further follow-up. CONCLUSION: While demanding of considerable time and effort, the return of clinically actionable genetic results is important from both an ethical perspective and to provide an improved trust relationship with the community of research participants.

Implementation fidelity of the Promoting First Relationships intervention program in a Native community.

Promoting First Relationship (PFR) is an evidence-based intervention designed to promote positive, supportive relationships between primary caregivers and their young children. Implementing and testing the efficacy of PFR in a remote Native community is especially challenging and requires methods and tools for ensuring implementation fidelity. Tribal members of a Native community were successfully trained and certified to deliver PFR by university-based personnel. During PFR delivery, they achieved very high scores on adherence to intervention content (M = 0.99, SD = 0.02), and their quality of delivery uniformly exceeded established criteria. High attrition occurred before PFR was delivered. However, participants who remained in the study completed all 10 sessions of PFR content. Participants' satisfaction with the program was very high (M = 3.90 [of 4 points], SD = 0.19). High implementation fidelity was attained in the face of many inherent challenges. The suite of methods and tools used for training, monitoring, and evaluating implementation fidelity in this study provides an example that may be useful in the evaluation of evidence-based programs more generally.

Promoting First Relationships® for Primary Caregivers and Toddlers in a Native Community: a Randomized Controlled Trial.

This study tested the effectiveness of Promoting First Relationships® (PFR), a preventive intervention program aimed at fostering positive caregiver-child relationships in Native families living on a rural reservation. Participants were 162 primary caregivers (96% Native; 93% female) and their Native toddlers (10-31 months old; 50% female). Families were randomized to a PFR group (n = 81) or Resource and Referral (RR) control group (n = 81), after baseline data collection (Time 1) to assess the quality of caregiver-child interaction, caregiver knowledge about children's social-emotional needs, caregiver depressive symptoms, and child externalizing behavior. After delivery of the PFR intervention or the RR service, follow-up assessments were repeated immediately post-intervention (Time 2) and 3 months later (Time 3). After controlling for baseline assessments, multivariate analyses of covariance revealed that caregivers in the PFR group had significantly higher scores on knowledge about children's social-emotional needs at Time 2 (p < .01, η2 = .06) and Time 3 (p < .05, η2 = .04) and less severe depressive symptoms at Times 2 and 3 (both p < .05, η2 = .04). At Time 3, the quality of caregiver-child interaction was better in the PFR group (p < .01, η2 = .06), an effect that was moderated by severity of depressive symptoms (p = .05, η2 = .06), with PFR having the greatest impact at low levels of initial symptoms (p = .02). Results support the positive impact of PFR in a Native community and suggest conditions under which the intervention may be most effective.

Efficacy and feasibility of the BREATHE asthma intervention with American Indian children: a randomized controlled trial.

American Indian (AI) children experience significant disparities in asthma prevalence, severity, and burden of disease, yet few asthma education interventions are tested in this population. This study aimed to evaluate the efficacy and feasibility of the BREATHE intervention with parents and AI children, during a 3-year follow-up period (n = 108), using a randomized controlled design. Children with asthma identified by electronic medical records (EMR) were screened and matched with 2 controls. The intervention included an initial educational and 24 months of follow-up. The control group continued their usual care. The primary outcome was the frequency of EMR documented, emergency department (ED) visits or hospitalization for respiratory complaints. There was no statistical difference in mean primary outcomes (1.34 (1.98) vs 1.22 (1.95), - 0.88 to 0.63, 95% CI of the difference, p = 0.75), nor percent with any ED visit or hospitalization (29/53, 55% vs 30/55, 54%, p = 0.99) between the intervention or control groups respectively. After 365 days, there was a borderline significant difference in time to primary outcome. Although limited in power, the present study did not demonstrate a persistent effect of this intervention. We recommend that AI pediatric asthma interventions are culturally-designed, use feasible procedures, and repeat education at least every 12 months.

Experiences of Native Participants in the Promoting First Relationships® Intervention: Focus Group Findings.

OBJECTIVES: We tested Promoting First Relationships® (PFR), an evidence-based preventive intervention program for caregivers promoting attachment and social and emotional development of infants and toddlers, in a randomized controlled trial in a Native community. Quantitative results yielded evidence of efficacy; but in this report, our objective was to assess the participants' real-life experiences, challenges, and suggested enhancements to further adapt the program. METHODS: At the end of the study we conducted three focus groups (N = 17)-two groups for participants who completed the 10-week intervention and one group for those who did not. Focus groups were structured to generate discussion about (1) elements or activities of PFR they enjoyed and others that were challenging, (2) suggested solutions to participant challenges, (3) experiences with video recordings and handouts, and (4) aspects of the program that could be changed to make it more culturally-relevant. RESULTS: Qualitative analysis of the focus group transcripts revealed five themes: (1) appreciation for PFR providers and program, (2) personal growth, (3) improved caregiver-child relationships, (4) participant challenges, and (5) participant suggestions to improve the program. CONCLUSIONS: These qualitative results complement our quantitative assessment of the positive impact of the PFR program. Additionally, they provide importance guidance for future implementation of PFR in this, and other Native communities, as well as insight into broader issues to consider when adapting intervention programs for Native families.

Active smoking, secondhand smoke exposure and serum cotinine levels among Cheyenne River Sioux communities in context of a Tribal Public Health Policy.

INTRODUCTION: American Indians and Alaska Natives face disproportionately high rates of smoking and secondhand smoke (SHS) exposure. The Cheyenne River Sioux Tribe (CRST) is among the few Tribal Nations controlling commercial tobacco exposures in public and work places. We had an opportunity to explore effects of the new commercial tobacco-free policy (implemented in 2015) in an environmental health study (2014-2016) that collected information about commercial tobacco use and SHS prevalence and examined predictor variables of serum cotinine concentrations. METHODS: Self-reported survey data were used in quantile regression statistical modelling to explore changes in cotinine levels, based on smoking status, smokeless tobacco consumption and SHS exposure. RESULTS: From enrolled 225 adults, 51% (N=114) were current smokers. Among 88 non-tobacco users, 35 (40%) reported current SHS exposure. Significant differences in cotinine median concentrations were found among participants with and without current SHS exposure. Extremely high cotinine concentrations (~100 times larger than the median) were detected in some non-tobacco users. After implementing the new smoke-free air Tribal policy, cotinine decreased in participants with intermediate (3-15 ng/mL, non-tobacco users with SHS exposure) and high (>15 ng/mL, mainly tobacco users) cotinine levels showing association with an abatement of opportunities for SHS exposure. Significant predictors of cotinine levels were sampling year, current smoking and tobacco chewing. No gender differences were observed in cotinine. CONCLUSIONS: Our results show decrease in cotinine concentrations in CRST participants since implementation of their 'Smoke-Free Clean Air Act' in 2015.

Using Goal Setting and Attainment to Impact Indicators of Health Behavior Change among Young American Indian Women: The We RISE (Raising Income, Supporting Education) Study.

The purpose of the present study was to assess the association between setting and attaining goals and indicators of health behavior change (psychological general well-being index, self-efficacy, and health locus of control) among young American Indian mothers. A total of 60 women were randomized to either intervention or control. At the end of the 6-month intervention, goal attainment was not significantly associated with the three outcomes of interest. However, resource program contacts and goal track were associated with confidence in completing goals and health locus of control internality, respectively. Lessons learned and future research needs are discussed.

Developing the Tribal Resource Guide and the Poverty and Culture Training: The We RISE (Raising Income, Supporting Education) Study.

The We RISE Study aimed to support young American Indian mothers on a tribal reservation by addressing social determinants of health at an individual and community-wide level. To address community-based barriers, the study developed the Tribal Resource Guide, a comprehensive list of available resources that was created through partnerships with community programs and staff. In addition to the guide, the study also developed the Poverty and Culture Training in order to train program staff at numerous community programs to better understand and serve lower socioeconomic and/or Native clients. The two projects facilitated collaboration between community programs and provided tools for programs to address barriers and ultimately better serve their target audience. Despite challenges, the transdisciplinary approach used with the local community maximized potential for success. This process and model could be duplicated in communities with similar demographics, resources, and barriers.

Dietary determinants of inorganic arsenic exposure in the Strong Heart Family Study.

BACKGROUND: Chronic exposure to inorganic arsenic (iAs) in the US occurs mainly through drinking water and diet. Although American Indian (AI) populations have elevated urinary arsenic concentrations compared to the general US population, dietary sources of arsenic exposure in AI populations are not well characterized. METHODS: We evaluated food frequency questionnaires to determine the major dietary sources of urinary arsenic concentrations (measured as the sum of arsenite, arsenate, monomethylarsonate, and dimethylarsinate, ΣAs) for 1727 AI participants in the Strong Heart Family Study (SHFS). We compared geometric mean ratios (GMRs) of urinary ΣAs for an interquartile range (IQR) increase in reported food group consumption. Exploratory analyses were stratified by gender and study center. RESULTS: In fully adjusted generalized estimating equation models, the percent increase (95% confidence interval) of urinary ΣAs per increase in reported food consumption corresponding to the IQR was 13% (5%, 21%) for organ meat, 8% (4%, 13%) for rice, 7% (2%, 13%) for processed meat, and 4% (1%, 7%) for non-alcoholic drinks. In analyses stratified by study center, the association with organ meat was only observed in North/South Dakota. Consumption of red meat [percent increase -7% (-11%, -3%)] and fries and chips [-6% (-10%, -2%)] was inversely associated with urinary ΣAs. CONCLUSIONS: Organ meat, processed meat, rice, and non-alcoholic drinks contribute to ΣAs exposure in the SHFS population. Organ meat is a unique source of ΣAs exposure for North and South Dakota participants and may reflect local food consumption. Further studies should comprehensively evaluate drinking water arsenic in SHFS communities and determine the relative contribution of diet and drinking water to total arsenic exposure.

Socioeconomic and Environmental Risk Factors for Pediatric Asthma in an American Indian Community.

BACKGROUND: American Indian (AI)/Alaska Native children have increased asthma prevalence, morbidity, and mortality compared to non-Hispanic white children. Our study sought to examine environmental and socioeconomic factors of asthma among children in an AI community. METHODS: This case-control study included children with physician-diagnosed asthma and age-matched controls, ages 6 through 17 years, in an AI community. Diagnosis and clinical characteristics were obtained from medical record review. Home visits included interviews regarding sociodemographic and household environmental exposures, physical exams, spirometry, and asthma control questionnaires (cases only). RESULTS: Among the 108 asthma cases and 215 controls, 64% had an annual household income of <$25,000. Children with asthma had significantly higher odds of living in a multi-unit dwelling (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2-4.4) or in residences with rodent or insect infestation (OR, 2.1; 95% CI, 1.1-3.8) and were less likely to live in homes with more than 8 occupants (OR, 0.5; 95% CI, 0.3-0.9). Also, there was a trend for lower caregiver education level, unmarried caregiver marital status, and annual household income level of <$25,000 in univariate analysis. However, after adjustment for socioeconomic status and household environmental factors, these estimates were not significant. Nearly half of cases had poorly controlled asthma and reported persistent cough, wheeze, and dyspnea, yet only 24% reported using a controller medication. CONCLUSIONS: In this low-income AI community, we identified several social and environmental determinants of asthma, which were mediated by socioeconomic status and other household environmental factors, suggesting a complex interplay between socioeconomic status and environmental exposures. Furthermore, many children with asthma reported poor asthma control.

Genetic variants and risk of asthma in an American Indian population.

BACKGROUND: Asthma is recognized as a complex, multifactorial disease with a genetic component that is well recognized. Certain genetic variants are associated with asthma in a number of populations. OBJECTIVE: To determine whether the same variants increase the risk of asthma among American Indian children. METHODS: The electronic medical records of an Indian Health Service facility identified all children between 6 and 17 years of age with case-defining criteria for asthma (n = 108). Control children (n = 216), matched for age, were also identified. Real-time polymerase chain reaction assays were used to genotype 10 single-nucleotide polymorphisms (SNPs) at 6 genetic loci. Genotypic distributions among cases and controls were evaluated by χ2 and logistic regression methods. RESULTS: A variant at 5q22.1 revealed a statistically significant imbalance in the distribution of genotypes between case-control pairs (rs10056340, P < .001). In logistic regression analyses, the same variant at 5q22.1 and a variant at 17q21 were associated with asthma at P < .05 (rs10056340 and rs9303277). Inclusions of age, body mass index, and atopy in multivariate models revealed significant associations between rs10056340 (odds ratio, 2.020; 95% confidence interval, 1.283-3.180; P = .002) and all 5 17q21 SNPs and asthma in this population. In analyses restricted to atopic individuals, the association of rs10056340 was essentially unchanged, whereas among nonatopic individuals the trend was in the same direction but nonsignificant. The reverse was true for the 17q21 SNPs. CONCLUSION: These findings demonstrate that many variants commonly associated with asthma in other populations also accompany this condition among American Indian children. American Indian children also appear to have an increased risk of asthma associated with obesity.

Humoral immune factors and asthma among American Indian children: a case-control study.

BACKGROUND: Asthma is recognized as intimately related to immunologic factors and inflammation, although there are likely multiple phenotypes and pathophysiologic pathways. Biomarkers of inflammation may shed light on causal factors and have potential clinical utility. Individual and population genetic factors are correlated with risk for asthma and improved understanding of these contributions could improve treatment and prevention of this serious condition. METHODS: A population-based sample of 108 children with clinically defined asthma and 216 control children were recruited from a small community in the northern plains of the United States. A complete blood count, high sensitivity C-reactive protein, total IgE and specific antibodies to 5 common airborne antigens (CAA), in addition to basic demographic and anthropomorphic data were obtained. Logistic regression was primarily used to determine the association between these humoral factors and risk of asthma. RESULTS: The body mass index (BMI) of those with asthma and their total leukocyte counts, percentage of eosinophils, and levels of total IgE were all greater than corresponding control values in univariate analysis. The presence of detectable, specific IgE antibodies to five common airborne antigens was more likely among cases compared with controls. In multivariate analysis, total IgE was independently associated with asthma; but not after inclusion of a cumulative measure of specific IgE sensitization. CONCLUSION: Many previously reported associations between anthropomorphic and immune factors and increased risk of asthma appear to be also present in this American Indian population. In this community, asthma is strongly associated with sensitization to CAA.

Asthma triggers on the Cheyenne River Indian Reservation in western South Dakota: the Breathing Relief Education and Tribal Health Empowerment (BREATHE) Study.

BACKGROUND: The purpose of this article is to better understand asthma triggers and possible causes of exacerbations among BREATHE participants on the Cheyenne River Indian Reservation in western South Dakota. METHODS: To qualify for enrollment, participants had to have physician-diagnosed asthma, be uncontrolled and have persistent symptoms. Participants were asked to identify their top two asthma triggers throughout their one-year enrollment during initial visits and subsequent phone follow-ups. In addition, participant's medical records were reviewed for visits to the emergency department (ED) to demonstrate asthma exacerbations. RESULTS: In 2008, 127 interviews were conducted with 45 enrolled participants for a total of 254 results. Overall, the three most common self reported triggers were cold air, dust and smoke and these comprised nearly half (48.4 percent) of all reports. Dust was reported in 16.5 percent of interviews and ranked among the top four for every season. Smoke (12.6 percent) and cold air (19.3 percent) were leaders in all seasons except summer, but humid air, pollens and strong odors were unique to summer. Exercise/activity ranked high during the winter and spring, but was reported less in summer and fall. There was no identifiable trend in ER visits by season. CONCLUSION: People with asthma living on the Cheyenne River Indian Reservation or other locations with similar community and geographic demographics are most likely to suffer an asthma exacerbation from exposure to cold air, dust, smoke and exercise/activity. Asthma education is necessary on all levels, but information on avoidance and control of these most common reported triggers is especially important.