Psychometric reliability, validity, and generalizability of 3MSE scores among American Indian adults: the Strong Heart Study.

OBJECTIVE: Modified Mini-Mental State Examination (3MSE) is often used to screen for dementia, but little is known about psychometric validity in American Indians. METHODS: We recruited 818 American Indians aged 65-95 for 3MSE examinations in 2010-2013; 403 returned for a repeat examination in 2017-2019. Analyses included standard psychometrics inferences for interpretation, generalizability, and extrapolation: factor analysis; internal consistency-reliability; test-retest score stability; multiple indicator multiple cause structural equation models. RESULTS: This cohort was mean age 73, majority female, mean 12 years education, and majority bilingual. The 4-factor and 2nd-order models fit best, with subfactors for orientation and visuo-construction (OVC), language and executive functioning (LEF), psychomotor and working memory (PMWM), verbal and episodic memory (VEM). Factor structure was supported for both research and clinical interpretation, and factor loadings were moderate to high. Scores were generally consistent over mean 7 years. Younger participants performed better in overall scores, but not in individual factors. Males performed better on OVC and LEF, females better on PMWM. Those with more education performed better on LEF and worse on OVC; the converse was true for bilinguals. All differences were significant, but small. CONCLUSION: These findings support use of 3MSE for individual interpretation in clinic and research among American Indians, with moderate consistency, stability, reliability over time. Observed extrapolations across age, sex, education, and bilingual groups suggest some important contextual differences may exist.

Psychometric Properties of Controlled Oral Word Association (COWA) Test and Associations With Education and Bilingualism in American Indian Adults: The Strong Heart Study.

The Controlled Oral Word Association (COWA) test is used to assess phonemic fluency and executive function. Formal validation of test scores is important for accurate cognitive evaluation. However, there is a dearth of psychometric validation among American Indian adults. Given high burden of dementia risk and key contextual factors associated with cognitive assessments, this represents a critical oversight. In a large, longitudinal population-based cohort study of adult American Indians, we examined several validity inferences for COWA, including scoring, generalization, and extrapolation inferences, by investigation of factor structure, internal consistency, test-retest reliability, and differential test functioning. We found adequate unidimensional model fit, with high factor loadings. Internal consistency reliability and test-retest reliability were 0.88 and 0.77, respectively, for the full group. COWA scores were lowest among the oldest, lowest education, bilingual speakers; group effects for sex and bilingual status were small; age effect was medium; and education effect was largest. However, Wide Range Achievement Test (WRAT) score effect was stronger than education effect, suggesting better contextualization may be needed. These results support interpretation of total COWA score, including across sex, age, or language use strata.

"Sorry for laughing, but it's scary": humor and silence in discussions of Colorectal Cancer with Urban American Indians.

BACKGROUND: Given high rates of cancer mortality in Native communities, we examined how urban American Indian and Alaska Native elders talk about colorectal cancer (CRC) and CRC screening. METHODS: We conducted seven focus groups with a total of 46 participants in two urban clinics in the Pacific Northwest to assess participant awareness, perceptions, and concerns about CRC and CRC screening. Using speech codes theory, we identified norms that govern when and how to talk about CRC in this population. RESULTS: Our analyses revealed that male participants often avoided screening because they perceived it as emasculating, whereas women often avoided screening because of embarrassment and past trauma resulting from sexual abuse. Both men and women used humor to mitigate the threatening nature of discussions about CRC and CRC screening. CONCLUSIONS: We offer our analytic results to assist others in developing culturally appropriate interventions to promote CRC screening among American Indians and Alaska Natives.

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

Evaluation of an experiential training program in patient-centered outcomes and comparative effectiveness research for diverse researcher communities and health care organizations.

Background/Objective: The goal of the Patient-Centered Outcomes Research Partnership was to prepare health care professionals and researchers to conduct patient-centered outcomes and comparative effectiveness research (CER). Substantial evidence gaps, heterogeneous health care systems, and decision-making challenges in the USA underscore the need for evidence-based strategies. Methods: We engaged five community-based health care organizations that serve diverse and underrepresented patient populations from Hawai'i to Minnesota. Each partner nominated two in-house scholars to participate in the 2-year program. The program focused on seven competencies pertinent to patient-centered outcomes and CER. It combined in-person and experiential learning with asynchronous, online education, and created adaptive, pragmatic learning opportunities and a Summer Institute. Metrics included the Clinical Research Appraisal Inventory (CRAI), a tool designed to assess research self-efficacy and clinical research skills across 10 domains. Results: We trained 31 scholars in 3 cohorts. Mean scores in nine domains of the CRAI improved; greater improvement was observed from the beginning to the midpoint than from the midpoint to conclusion of the program. Across all three cohorts, mean scores on 52 items (100%) increased (p ≤ 0.01), and 91% of scholars reported the program improved their skills moderately/significantly. Satisfaction with the program was high (91%). Conclusions: Investigators that conduct patient-centered outcomes and CER must know how to collaborate with regional health care systems to identify priorities; pose questions; design, conduct, and disseminate observational and experimental research; and transform knowledge into practical clinical applications. Training programs such as ours can facilitate such collaborations.

Trends in Alzheimer Disease Mortality Among American Indian and Alaska Native People Between 2011 and 2019.

PURPOSE: The number of American Indian and Alaska Native (AI/AN) people living with dementia is expected to increase 5-fold by 2060. Social determinants of health may explain disparities in the incidence of Alzheimer disease (AD) but remain largely overlooked. METHODS: We examined the time trend of AD mortality rates and associations of the percentage of AI/ANs, density of primary care physicians and neurologists, area deprivation index, rurality, and Indian Health Service region with AD mortality in 646 purchased/referred care delivery area counties. RESULTS: AD mortality rates significantly increased over time. Counties with higher concentrations of AI/AN people had lower AD mortality. More deprived counties had 34% higher AD mortality compared with less deprived counties. AD mortality was 20% lower in nonmetro counties than in metro counties. CONCLUSIONS: Findings have implications for prioritizing areas where more resources for AD care, education, or outreach are needed.

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.

Volume atrophy in medial temporal cortex and verbal memory scores in American Indians: Data from the Strong Heart Study.

INTRODUCTION: Distinguishing Alzheimer's disease (AD) patient subgroups may optimize positive clinical outcomes. Cortical atrophy is correlated with memory deficits, but these associations are understudied in American Indians. METHODS: We collected imaging and cognition data in the Strong Heart Study (SHS), a cohort of 11 tribes across three regions. We processed 1.5T MRI using FreeSurfer and iterative principal component analysis. Linear mixed models estimated volumetric associations with diabetes. RESULTS: Over mean 7 years follow-up (N = 818 age 65-89 years), overall volume loss was 0.5% per year. Significant losses associated with diabetes were especially strong in the right hemisphere. Annualized hippocampal, parahippocampal, entorhinal atrophy were worse for men, older age, diabetes, hypertension, stroke; and associated with both encoding and retrieval memory losses. DISCUSSION: Our findings suggest that diabetes is an important risk factor in American Indians for cortical atrophy and memory loss. Future research should examine opportunities for primary prevention in this underserved population.

Educational and Clinical Associations With Longitudinal Cognitive Function and Brain Imaging in American Indians: The Strong Heart Study.

BACKGROUND: Little is known about incidence of vascular and Alzheimer's dementias in American Indians. METHODS We conducted a large, heterogeneous, population-based, longitudinal cohort study of brain aging in community-dwelling American Indians aged 64-95 years from 11 tribes across 3 states, with neurological examinations, 1.5T magnetic resonance imaging (MRI), and extensive cognitive testing. Visit 1 in 2010-2013 (n=817) and Visit 2 in 2017-2019 (n=403) included all willing, surviving participants. Standardized cognitive tests at both visits included Modified Mini Mental Status Examination (3MSE), Wechsler Adult Intelligence Scale digit symbol coding (WAIS), Controlled Oral Word Association fas (COWA), California Verbal Learning Test short form (CVLT). Test materials added at follow-up included Wide Range Achievement (reading) Test (WRAT) and National Alzheimer's Coordinating Center Uniform Data Set cognitive battery (v3 form C2) , including Montreal Cognitive Assessment (MoCA). MRI neuroradiologists coded infarcts, hemorrhages, white matter hyperintensities, sulcal atrophy, and ventricle enlargement. RESULTS Mean time between exams was 6.7 years (SD 1.1, range 3.8-9.1). Years of formal education had modest correlation with WRAT reading score (r=0.45). Prevalence and incidence of infarcts were (respectively) 32% and 12.8/1000 person-years (PY); hemmorhages 6% and 4.4/1000 PY; worsening sulci 74% and 19.0/1000 PY; wosening ventricle 79% and 30.1/1000 PY; worsening leukoaraiosis 44% and 26.1/1000 PY. Linear losses per year in cognitive scores were 0.6% 3MSE, 1.2% WAIS, 0.6% COWA, 2.2% CVLT. Mean MoCA scores were 18.9 (SD 4.3). DISCUSSION These are the first data on longitudinal cognitive and imaging changes in American Indians, as well as first reports of AD related features. Mean scores in MoCA were similar or lower than standard cutoffs used to diagnose dementia in other racial/ethnic groups, suggesting that standardized cognitive tests may not perform well in this population. Test validation, adaptation, and score adjustment are warranted. Years of education was a poor proxy for premorbid function, suggesting novel methods for cognitive score contextualization is also needed in this population. Evaluation of selective survival suggests attrition from death and frailty should be accounted for in causal analyses. Overall, these data represent a unique opportunity to examine neurology topics of critical importance to an understudied population.

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.

Deaths associated with opioids, race and ethnicity, and years of potential life lost in Washington State.

INTRODUCTION: This study examined disparities in years of potential life lost (YPLL) related to opioid use among racial and ethnic groups adjusting for individual- and neighborhood-level characteristics. METHODS: The study obtained data on 5265 geocoded death records associated with opioid use from the Washington State Department of Health. Death certificates included information on race and ethnicity, sex, marital status, and educational attainment. We linked these records to neighborhood-level indicators of rurality, area deprivation, and access to opioid treatment programs. Generalized linear mixed models tested associations between racial and ethnic identity and YPLL controlling for other individual and neighborhood characteristics. RESULTS: Among all decedents from opioid-related causes, the study found that racial and ethnic minorities-including Black, American Indian/Alaska Native, Asian, Native Hawaiian or other Pacific Islander-multiracial, or Hispanic adults died at younger ages than did White adults (33 to 44 vs 45). In the fully adjusted models, the estimated mean for YPLL was higher for Asian or Native Hawaiian or other Pacific Islander, multiracial, and Hispanic adults compared to White adults. Accounting for educational attainment and marital status substantially reduced YPLL differences between groups, by as much as 40% in some cases. CONCLUSIONS: The study observed striking differences in YPLL related to opioid causes among racial and ethnic minorities. Accounting for social determinants of health greatly reduced YPLL across all groups but racial and ethnic disparities in YPLL remained significant. Understanding and alleviating additional causes of disparities in YPLL is warranted to abate the epidemic of opioid related deaths in the United States.

Disparities in Access to Radiation Therapy by Race and Ethnicity in the United States With Focus on American Indian/Alaska Native People.

OBJECTIVES: Striking disparities in access to radiation therapy (RT) exist, especially among racial and ethnic-minority patients. We analyzed census block group data to evaluate differences in travel distance to RT as a function of race and ethnicity, socioeconomic status, and rurality. METHODS: The Directory of Radiotherapy Centers provided the addresses of facilities containing linear accelerators for RT. We classified block groups as majority (≥ 50%) American Indian/Alaska Native (AI/AN), black, white, Asian, no single racial majority, or Hispanic regardless of race. We used the Area Deprivation Index to classify deprivation and Rural-Urban Commuting Area codes to classify rurality. Generalized linear mixed models tested associations between these factors and distance to nearest RT facility. RESULTS: Median distance to nearest RT facility was 72 miles in AI/AN-majority block groups, but 4 to 7 miles in block groups with non-AI/AN majorities. Multivariable models estimated that travel distances in AI/AN-majority block groups were 39 to 41 miles longer than in areas with non-AI/AN majorities. Travel distance was 1.3 miles longer in the more deprived areas versus less deprived areas and 16 to 32 miles longer in micropolitan, small town, and rural areas versus metropolitan areas. CONCLUSIONS: Cancer patients in block groups with AI/AN-majority populations, nonmetropolitan location, and low socioeconomic status experience substantial travel disparities in access to RT. Future research with more granular community- and individual-level data should explore the many other known barriers to access to cancer care and their relationship to the barriers posed by distance to RT care.

Associations of Binge Drinking With Vascular Brain Injury and Atrophy in Older American Indians: The Strong Heart Study.

Objectives: American Indians (AIs) generally consume less alcohol than the US general population; however, the prevalence of alcohol use disorder is higher. This is the first large cohort study to examine binge drinking as a risk factor for vascular brain injury (VBI). Methods: We used linear and Poisson regression to examine the association of self-reported binge drinking with VBI, measured via magnetic resonance imaging (MRI), in 817 older AIs who participated in the Strong Heart and Cerebrovascular Disease and Its Consequences in American Indians studies. Results: Any binge drinking at multiple time-points was associated with increased sulcal (ß = 0.360, 95% CI [0.079, 0.641]) and ventricle dilatation (ß = 0.512, 95% CI [0.174, 0.850]) compared to no binge drinking. Discussion: These observed associations are consistent with previous findings. Identifying how binge drinking may contribute to VBI in older AIs may suggest modifiable health behaviors for neurological risk reduction and disease prevention.

Aging and Health of American Indians and Alaska Natives: Contributions from the Native Investigator Development Program.

Objectives: To describe recent advances in our knowledge regarding the health and illness of older American Indians and Alaska Natives, and factors underlying why this special population lives 5.5 years less than the 78.5 years of U.S. all races. Methods: The articles in this supplemental issue, authored by participants in a National Institutes of Health-sponsored early research career development program, examine high priority health concerns that contribute to the increased risk of Native elders for chronic disease and resulting impairment that compromise their life expectancy. Results: Important insights into the roles that racial discrimination, food security, hypertension, alcohol consumption, memory problems, and military service play in the health and well-being of older American Indians and Alaska Natives. Discussion: Early career faculty development programs focused on increasing the diversity of the scientific workforce not only promote greater racial and ethnic minority representation in the field of aging, but can simultaneously add to the knowledge base regarding the health status and function of often ignored, vulnerable older members of communities that suffer significant health disparities.

Home Blood Pressure Monitoring Devices: Device Performance in an Alaska Native and American Indian Population.

Objectives: Home blood pressure monitoring (HBPM) is an important component of blood pressure (BP) management. We assessed performance of two HBPM devices among Alaska Native and American Indian people (ANAIs). Methods: We measured BP using Omron BP786 arm cuff, Omron BP654 wrist cuff, and Baum aneroid sphygmomanometer in 100 ANAIs. Performance was assessed with intraclass correlation, paired t-tests, and calibration models. Results: Compared to sphygmomanometer, average BP was higher for wrist cuff (systolic = 4.8 mmHg and diastolic = 3.6 mmHg) and varied for arm cuff (systolic = -1.5 mmHg and diastolic = 2.5 mmHg). Calibration increased performance from grade B to A for arm cuff and from D to B for wrist cuff. Calibration increased false negatives and decreased false positives. Discussion: The arm HBPM device is more accurate than the wrist cuff among ANAIs with hypertension. Most patients are willing to use the arm cuff when accuracy is discussed.

Glomerular filtration function decline, mortality, and cardiovascular events: data from the Strong Heart Study.

BACKGROUND: Rapid kidney decline is associated with mortality and cardiovascular disease, even in the absence of chronic kidney disease. American Indians (AI) have particularly high burden of kidney disease, cardiovascular disease, and stroke. This study aims to examine extreme loss in glomerular function in this population in association with clinical outcomes. METHODS: The Strong Heart Study, a large longitudinal cohort of adult AI participants, collected plasma creatinine at 3 examination visits between 1989-1999. Intraindividual regressions of estimated glomerular filtration rate (eGFR) provided linear estimates of change in kidney function over this time period. Surveillance with physician adjudication identified mortality and cardiovascular events between visit 3 through 2017. RESULTS: Mean change in eGFR was loss 6.8 mL/min over the ten year baseline (range: -66.0 to +28.9 mL/min). The top 1 percentile lost approximately 5.7 mL/min/year. Participants with extreme eGFR loss were more likely to have diabetes (95% vs 71%), hypertension (49% vs 33%), or longer smoking history, among smokers (19 pack years vs 17 pack years). CKD (eGFR<60 mL/min) was associated only with mortality, independent of slope: HR 1.1 (95% CI 1.0-1.3). However, extreme loss in eGFR (>20 mL/min over baseline period) was associated with mortality, independent of baseline eGFR: HR 3.5 (95% CI 2.7-4.4), and also independently associated with composite CVD events and CHF: HR 1.4 and 1.7 (95% CI 1.1-1.9 and 1.2-2.6), respectively. CONCLUSION: This is the first examination of decline in eGFR in association with mortality and CVD among AIs. The implications of these findings are broad: clinical evaluation may benefit from evaluating change in eGFR over time in addition to dichotomous eGFR. Also, these findings suggest there may be aspects of renal function that are not well-marked by clinical CKD, but which may have particular relevance to long-term renal and vascular health.

Increasing health equity through biospecimen research: Identification of factors that influence willingness of Native Americans to donate biospecimens.

American Indian and Alaska Native (AI/AN) people are underrepresented in biomedical research, particularly in biospecimen research, yet little research has been conducted to assess AI/AN attitudes about biospecimen donation. Survey data were collected from 278 AI/AN people in Seattle, Washington in 2016 to assess general willingness to donate, background characteristics related to willingness, and circumstances that would increase or decrease willingness to donate biospecimens. Less than half (43%) of participants were willing to donate. General willingness was related to past donation, and trust in how researchers use and store biospecimens. However, willingness to donate for cancer research was 76%. Fear of research exploitation and spiritual beliefs decreased willingness. Among those who were generally unwilling to donate, willingness increased if the biobank was run by a Native American organization, if the participant or family member had cancer and this was the disease being studied, if the community was involved in developing, reviewing, and approving the research, and if the expertise of researchers was known. Among those who were willing, willingness decreased if they had never heard of the research organization, and if the biobank was run by the federal government. Participation of AI/AN people in biobanking initiatives is critical to address health inequities and improve the health of AI/AN people, realize personalized medicine goals, and address the limited generalizability of current clinical and biospecimen research. These results highlight areas in which interventions could be developed to increase AI/AN donation of biospecimens for research with the ultimate goal of reducing health disparities.

Genetic and environmental influences on posttraumatic stress disorder symptoms and disinhibited eating behaviors.

Posttraumatic stress disorder (PTSD) and eating disorders (ED) frequently co-occur, but the mechanisms underlying this association remain unclear. EDs are characterized by features of maladaptive eating behaviors including disinhibited eating and cognitive dietary restraint. Identifying the genetic overlap between PTSD symptoms and maladaptive eating behaviors may elucidate biological mechanisms and potential treatment targets. A community sample of 400 same-sex twins (102 monozygotic and 98 dizygotic pairs) completed the PTSD Checklist-Civilian (PCL-C) for PTSD symptoms and the Three-Factor Eating Questionnaire-Reduced (TFEQ-R18) for eating behaviors (uncontrolled eating, emotional eating, and cognitive dietary restraint). We used biometric modeling to examine the genetic and environmental relationships between PCL-C and TFEQ-R18 total and subscales scores. Heritability was estimated at 48% for PTSD symptoms and 45% for eating behavior overall. Bivariate models revealed a significant genetic correlation between PTSD symptoms and eating behavior overall (rg =.34; CI:.07,.58) and Uncontrolled Eating (rg =.53; CI:.24,.84), and a significant environmental correlation between PTSD symptoms and Emotional Eating (re =.30; CI:.12,.45). These findings suggest the influence of common etiology. Future research and clinical efforts should focus on developing integrated treatments.

Genetics of Smoking Behaviors in American Indians.

BACKGROUND: The smoking behavior of American Indians (AI) differs from that of non-Hispanic whites (NHW). Typically light smokers, cessation interventions in AIs are generally less effective. To develop more effective cessation programs for AIs, clinicians, researchers, and public health workers need a better understanding of the genetic factors involved in their smoking behavior. Our aim was to assess whether SNPs associated with smoking behavior in NHWs are also associated with smoking in AIs. METHODS: We collected questionnaire data on smoking behaviors and analyzed blood and saliva samples from two Tribal populations with dramatically different cultures and smoking prevalence, one in the Northern Plains (n = 323) and the other in the Southwest (n = 176). A total of 384 SNPs were genotyped using an Illumina custom GoldenGate platform. Samples were also assessed for cotinine and 3-hydroxycotinine as markers of nicotine intake and nicotine metabolite ratio. RESULTS: Among 499 participants, we identified, in the Northern Plains sample only, a variant of the gamma-aminobutyric acid receptor subunit alpha-2 (GABRA2) (rs2119767) on chromosome 4p that was associated with many of the intake biomarkers of smoking we examined, suggesting a role for this gene in modifying smoking behavior in this population. We also identified three SNPs, in the Southwest sample only, as significant correlates of only cigarettes per day: rs4274224, rs4245147 (both dopamine receptor D2 gene), and rs1386493 (tryptophan hydroxylase 2 gene). CONCLUSIONS: The contribution of many genes known to underlie smoking behaviors in NHWs may differ in AIs. IMPACT: Once validated, these variants could be useful in developing more effective cessation strategies.