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Timber Lake, SD, United States

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. Source


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. Source


Xu J.,Methodist Hospital Research Institute | Lee E.T.,The University of Oklahoma Health Sciences Center | Peterson L.E.,Methodist Hospital Research Institute | Devereux R.B.,New York Medical College | And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Coronary heart disease (CHD) is the leading cause of death in the United States. Objective: This study compares differences in risk factors for CHD in diabetic vs. nondiabetic Strong Heart Study participants. Design: This was an observational study. Setting: The study was conducted at three centers in Arizona, Oklahoma, and North and South Dakota. Participants: Data were obtained from 3563 of 4549 American Indians free of cardiovascular disease at baseline. Intervention(s): CHD events were ascertained during follow-up. Main Outcome Measure: CHD events were classified using standardized criteria. Results: In diabetic and nondiabetic participants, 545 and 216 CHD events, respectively, were ascertained during follow-up (21,194 and 22,990 person-years); age- and sex-adjusted incidence rates of CHD were higher for the diabetic group (27.5 vs. 12.1 per 1,000 person-years). Risk factors for incident CHD common to both groups included older age, male sex, prehypertension or hypertension, and elevated low-density lipoprotein cholesterol. Risk factors specific to the diabetic group were lower high-density lipoprotein cholesterol, current smoking, macroalbuminuria, lower estimated glomerular filtration rate, use of diabetes medication, and longer duration of diabetes. Higher body mass index was a risk factor only for the nondiabetic group. The association of male sex and CHD was greater in those without diabetes than in those with diabetes. Conclusions: In addition to higher incidence rates of CHD events in persons with diabetes compared with those without, the two groups differed in CHD risk factors. These differences must be recognized in estimating CHD risk and managing risk factors. Copyright © 2012 by The Endocrine Society. Source


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. Source


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. Source

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