Timber Lake, SD, United States
Timber Lake, SD, United States

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Yang J.,The University of Oklahoma Health Sciences Center | Zhu Y.,The University of Oklahoma Health Sciences Center | Cole S.A.,The Texas Institute | Haack K.,The Texas Institute | And 10 more authors.
Diabetes | Year: 2012

Cigarette smoking is a risk factor for type 2 diabetes. Genetic variants in the nicotinic acetylcholine receptor (nAChR) genes have been associated with smoking phenotypes and are likely to influence diabetes. Although each single variant may have only a minor effect, the joint contribution of multiple single nucleotide polymorphisms (SNPs) to the occurrence of disease may be larger. In this study, we conducted a gene-family analysis to investigate the joint impact of 61 tag SNPs in 7 nAChRs genes on insulin resistance and type 2 diabetes in 3,665 American Indians recruited by the Strong Heart Family Study. Results show that although multiple SNPs showed marginal individual association with insulin resistance and type 2 diabetes, only a few can pass adjustment for multiple testing. However, a gene-family analysis considering the joint impact of all 61 SNPs reveals significant association of the nAChR gene family with both insulin resistance and type 2 diabetes (both P < 0.0001), suggesting that genetic variants in the nAChR genes jointly contribute to insulin resistance and type 2 diabetes among American Indians. The effects of these genetic variants on insulin resistance and diabetes are independent of cigarette smoking per se. © 2012 by the American Diabetes Association.


Yang J.,Tulane University | Zhu Y.,Tulane University | Lee E.T.,The University of Oklahoma Health Sciences Center | Zhang Y.,The University of Oklahoma Health Sciences Center | And 8 more authors.
Circulation: Cardiovascular Genetics | Year: 2013

Background-Atherosclerosis is the underlying cause of cardiovascular disease, the leading cause of morbidity and mortality in all American populations, including American Indians. Genetic factors play an important role in the pathogenesis of atherosclerosis. Although a single-nucleotide polymorphism (SNP) may explain only a small portion of variability in disease, the joint effect of multiple variants in a pathway on disease susceptibility could be large. Methods and Results-Using a gene-family analysis, we investigated the joint associations of 61 tag SNPs in 7 nicotinic acetylcholine receptor genes with subclinical atherosclerosis, as measured by carotid intima-media thickness and plaque score, in 3665 American Indians from 94 families recruited by the Strong Heart Family Study (SHFS). Although multiple SNPs showed marginal association with intima-media thickness and plaque score individually, only a few survived adjustments for multiple testing. However, simultaneously modeling of the joint effect of all 61 SNPs in 7 nicotinic acetylcholine receptor genes revealed significant association of the nicotinic acetylcholine receptor gene family with both intima-media thickness and plaque score independent of known coronary risk factors. Conclusions-Genetic variants in the nicotinic acetylcholine receptor gene family jointly contribute to subclinical atherosclerosis in American Indians who participated in the SHFS. These variants may influence the susceptibility of atherosclerosis through pathways other than cigarette smoking per se. © 2013 American Heart Association, Inc.


Franceschini N.,University of North Carolina at Chapel Hill | Haack K.,The Texas Institute | Almasy L.,The Texas Institute | Laston S.,The Texas Institute | And 8 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2014

Background and objectives CKD disproportionally affects American Indians, who similar to other populations, show genetic susceptibility to kidney outcomes. Recent studies have identified several loci associated with kidney traits, but their relevance in American Indians is unknown. Design, setting, participants, & measurements This study used data from a large, family-based genetic study of American Indians (the Strong Heart Family Study), which includes 94 multigenerational families enrolled from communities located in Oklahoma, the Dakotas, and Arizona. Individuals were recruited from the Strong Heart Study, a population-based study of cardiovascular disease in American Indians. This study selected 25 single nucleotide polymorphisms in 23 loci identified from recently published kidney-related genome-wide association studies in individuals of European ancestry to evaluate their associations with kidney function (estimated GFR; individuals 18 years or older, up to 3282 individuals) and albuminuria (urinary albumin to creatinine ratio; n=3552) in the Strong Heart Family Study. This study also examined the association of single nucleotide polymorphisms in the APOL1 region with estimated GFR in 1121 Strong Heart Family Study participants. GFR was estimated using the abbreviated Modification of Diet in Renal Disease Equation. Additive genetic models adjusted for age and sex were used. Results This study identified significant associations of single nucleotide polymorphisms with estimated GFR in or nearby PRKAG2, SLC6A13, UBE2Q2, PIP5K1B, and WDR72 (P<2.1 × 10-3 to account for multiple testing). Single nucleotide polymorphisms in these loci explained 2.2% of the estimated GFR total variance and 2.9% of its heritability. An intronic variant of BCAS3 was significantly associated with urinary albumin to creatinine ratio. APOL1 single nucleotide polymorphisms were not associated with estimated GFR in a single variant test or haplotype analyses, and the at-risk variants identified in individuals with African ancestry were not detected in DNA sequencing of American Indians. Conclusion This study extends the genetic associations of loci affecting kidney function to American Indians, a population at high risk of kidney disease, and provides additional support for a potential biologic relevance of these loci across ancestries. © 2014 by the American Society of Nephrology.


Garcia-Esquinas E.,Johns Hopkins University | Garcia-Esquinas E.,U.S. National Cancer Institute | Garcia-Esquinas E.,Consortium for Biomedical Research in Epidemiology and Public Health | Pollan M.,U.S. National Cancer Institute | And 12 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2013

Background: Inorganic arsenic, a carcinogen at high exposure levels, is a major global health problem. rospective studies on carcinogenic effects at low-moderate arsenic levels are lacking. Methods: We evaluated the association between baseline arsenic exposure and cancer mortality in 3,932 American Indians, 45 to 74 years of age, from Arizona, Oklahoma, and North/South Dakota who participated in the Strong Heart Study from 1989 to 1991 and were followed through 2008. We estimated inorganic arsenic exposure as the sum of inorganic and methylated species in urine. Cancer deaths (386 overall, 78 lung, 34 liver, 18 prostate, 26 kidney, 24 esophagus/stomach, 25 pancreas, 32 colon/rectal, 26 breast, and 40 lymphatic/ hematopoietic) were assessed by mortality surveillance reviews. We hypothesized an association with lung, liver, prostate, and kidney cancers. Results: Median (interquartile range) urine concentration for inorganic plus methylated arsenic species was 9.7 (5.8-15.6) μg/g creatinine. The adjusted HRs [95% confidence interval (CI)] comparing the 80th versus 20th percentiles of arsenic were 1.14 (0.92-1.41) for overall cancer, 1.56 (1.02-2.39) for lung cancer, 1.34 (0.66, 2.72) for liver cancer, 3.30 (1.28-8.48) for prostate cancer, and 0.44 (0.14, 1.14) for kidney cancer. The corresponding hazard ratios were 2.46 (1.09-5.58) for pancreatic cancer, and 0.46 (0.22-0.96) for lymphatic and hematopoietic cancers. Arsenic was not associated with cancers of the esophagus and stomach, colon and rectum, and breast. Conclusions: Low to moderate exposure to inorganic arsenic was prospectively associated with increased mortality for cancers of the lung, prostate, and pancreas. Impact: These findings support the role of low-moderate arsenic exposure in development of lung, prostate, and pancreas cancer and can inform arsenic risk assessment. ©2013 American Association for Cancer Research.


Yeh F.,The University of Oklahoma Health Sciences Center | Dixon A.E.,University of Vermont | Marion S.,University of Delaware | Schaefer C.,The University of Oklahoma Health Sciences Center | And 5 more authors.
Diabetes Care | Year: 2011

OBJECTIVE - The purposes of this study were to investigate whether reduced lung function is associated with metabolic syndrome (MS) and diabetes (DM) in American Indians (AIs) and to determine whether lower pulmonary function presents before the development of DM or MS. RESEARCH DESIGN AND METHODS - The Strong Heart Study (SHS) is a multicenter, prospective study of cardiovascular disease (CVD) and its risk factors among AI adults. The present analysis used lung function assessment by standard spirometry at the SHS second examination (1993-1995) in 2,396 adults free of overt lung disease or CVD, with or without DM or MS. Among MS-free/DM-free participants, the development of MS/DM at the SHS third examination (1996-1999) was investigated. RESULTS - Significantly lower pulmonary function was observed for AIs with MS or DM. Impaired pulmonary function was associated with MS and DM after adjustment for age, sex, abdominal obesity, current smoking status, physical activity index, hypertension, and SHS field center. Both forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were negatively associated with insulin resistance or DM severity and with serummarkers of inflammation (P < 0.05). FVC and FEV1-to-FVC ratio both predicted DMin unadjusted analyses but not when adjusted for covariates, including waist circumference. In the adjustedmodel, abdominal obesity predicted both MS and DM. CONCLUSIONS - Reduced lung function is independently associated with MS and with DM, and impaired lung function presents before the development of MS or DM; these associations may result from the effects of obesity and inflammation. © 2011 by the American Diabetes Association.


Wang W.,The University of Oklahoma Health Sciences Center | Lee E.T.,The University of Oklahoma Health Sciences Center | Howard B.V.,MedStar Research Institute | Fabsitz R.R.,U.S. National Institutes of Health | And 2 more authors.
Diabetes Care | Year: 2011

OBJECTIVE - To compare fasting plasma glucose (FPG) and HbA 1c in identifying and predicting type 2 diabetes in a population with high rates of diabetes. RESEARCH DESIGN AND METHODS - Diabetes was defined as an FPG level ≥126 mg/dL or an HbA 1c level ≥6.5%. Data collected from the baseline and second exams (1989-1995) of the Strong Heart Study were used. RESULTS - For cases of diabetes identified by FPG ≥126 mg/dL, using HbA 1c ≥6.5% at the initial and 4-year follow-up diabetes screenings (or in identifying incident cases in 4 years) among undiagnosed participants left 46% and 59% of cases of diabetes undetected, respectively, whereas for cases identified by HbA 1c ≥6.5%, using FPG ≥126 mg/dL left 11% and 59% unidentified, respectively. Age, waist circumference, urinary albumin-to-creatinine ratio, and baseline FPG and HbA 1c levels were common significant risk factors for incident diabetes defined by either FPG or HbA 1c; triglyceride levels were significant for diabetes defined by HbA 1c alone, and blood pressure and sibling history of diabetes were significant for diabetes defined by FPG alone. Using both the baseline FPG and HbA 1c in diabetes prediction identifiedmore people at risk than using either measure alone. CONCLUSIONS - Among undiagnosed participants, using HbA 1c alone in initial diabetes screening identifies fewer cases of diabetes than FPG, and using either FPG or HbA 1c alone cannot effectively identify diabetes in a 4-year periodic successive diabetes screening or incident cases of diabetes in 4 years. Using both criteria may identify more people at risk. The proposed models using the commonly available clinical measures can be applied to assessing the risk of incident diabetes using either criterion. © 2011 by the American Diabetes Association.


Zhao J.,Tulane University | Zhu Y.,Tulane University | Lin J.,University of California at San Francisco | Matsuguchi T.,University of California at San Francisco | And 6 more authors.
Diabetes | Year: 2014

Telomeres play a central role in cellular aging, and shorter telomere length has been associated with age-related disorders including diabetes. However, a causal link between telomere shortening and diabetes risk has not been established. In a wellcharacterized longitudinal cohort of American Indians participating in the Strong Heart Family Study, we examined whether leukocyte telomere length (LTL) at baseline predicts incident diabetes independent of known diabetes risk factors. Among 2,328 participants free of diabetes at baseline, 292 subjects developed diabetes during an average 5.5 years of follow-up. Compared with subjects in the highest quartile (longest) of LTL, those in the lowest quartile (shortest) had an almost twofold increased risk of incident diabetes (hazard ratio [HR] 1.83 [95% CI 1.26-2.66]), whereas the risk for those in the second (HR 0.87 [95% CI 0.59-1.29]) and the third (HR 0.95 [95% CI 0.65-1.38]) quartiles was statistically nonsignificant. These findings suggest a nonlinear association between LTL and incident diabetes and indicate that LTL could serve as a predictive marker for diabetes development in American Indians, who suffer from disproportionately high rates of diabetes. © 2014 by the American Diabetes Association.


PubMed | University of Graz, Johns Hopkins University, University of Washington, MedStar Research Institute and Missouri Breaks Industries Research Inc.
Type: | Journal: Environmental research | Year: 2016

Natural and anthropogenic sources of metal exposure differ for urban and rural residents. We searched to identify patterns of metal mixtures which could suggest common environmental sources and/or metabolic pathways of different urinary metals, and compared metal-mixtures in two population-based studies from urban/sub-urban and rural/town areas in the US: the Multi-Ethnic Study of Atherosclerosis (MESA) and the Strong Heart Study (SHS).We studied a random sample of 308 White, Black, Chinese-American, and Hispanic participants in MESA (2000-2002) and 277 American Indian participants in SHS (1998-2003). We used principal component analysis (PCA), cluster analysis (CA), and linear discriminant analysis (LDA) to evaluate nine urinary metals (antimony [Sb], arsenic [As], cadmium [Cd], lead [Pb], molybdenum [Mo], selenium [Se], tungsten [W], uranium [U] and zinc [Zn]). For arsenic, we used the sum of inorganic and methylated species (As).All nine urinary metals were higher in SHS compared to MESA participants. PCA and CA revealed the same patterns in SHS, suggesting 4 distinct principal components (PC) or clusters (As-U-W, Pb-Sb, Cd-Zn, Mo-Se). In MESA, CA showed 2 large clusters (As-Mo-Sb-U-W, Cd-Pb-Se-Zn), while PCA showed 4 PCs (Sb-U-W, Pb-Se-Zn, Cd-Mo, As). LDA indicated that As, U, W, and Zn were the most discriminant variables distinguishing MESA and SHS participants.In SHS, the As-U-W cluster and PC might reflect groundwater contamination in rural areas, and the Cd-Zn cluster and PC could reflect common sources from meat products or metabolic interactions. Among the metals assayed, As, U, W and Zn differed the most between MESA and SHS, possibly reflecting disproportionate exposure from drinking water and perhaps food in rural Native communities compared to urban communities around the US.


Zhu Y.,Tulane University | Voruganti V.S.,The Texas Institute | Lin J.,University of California at San Francisco | Matsuguchi T.,University of California at San Francisco | And 6 more authors.
Aging | Year: 2013

Telomeres play a central role in cellular senescence and are associated with a variety of age-related disorders such as dementia, Alzheimer's disease and atherosclerosis. Telomere length varies greatly among individuals of the same age, and is heritable. Here we performed a genome-wide linkage scan to identify quantitative trait loci (QTL) influencing leukocyte telomere length (LTL) measured by quantitative PCR in 3,665 American Indians (aged 14-93 years) from 94 large, multi-generational families. All participants were recruited by the Strong Heart Family Study (SHFS), a prospective study to identify genetic factors for cardiovascular disease and its risk factors in American Indians residing in Oklahoma, Arizona and Dakota. LTL heritability was estimated to be between 51% and 62%, suggesting a strong genetic predisposition to interindividual variation of LTL in this population. Significant QTLs were localized to chromosome 13 (Logarithm of odds score (LOD) = 3.9) at 13q12.11, to 18q22.2 (LOD = 3.2) and to 3p14.1 (LOD = 3.0) for Oklahoma. This is the first study to identify susceptibility loci influencing leukocyte telomere variation in American Indians, a minority group suffering from a disproportionately high rate of type 2 diabetes and other age-related disorders. © Zhu et al.


O'Leary R.,Missouri Breaks Industries Research Inc.
South Dakota medicine : the journal of the South Dakota State Medical Association | Year: 2012

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. 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. 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. 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.

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