A genome-wide linkage and association study using COGA data

BACKGROUND: Genome-wide association will soon be available to use as an adjunct to traditional linkage analysis. We studied alcoholism in 119 families collected by the Collaborative Study on the Genetics of Alcoholism and made available in Genetic Analysis Workshop 14, using genome-wide linkage and association analyses. METHODS: Genome-wide linkage analysis was first performed using microsatellite markers and a region with the strongest linkage evidence was further analyzed using single-nucleotide polymorphisms (SNPs). Family based genome-wide association test was also conducted using the SNPs. RESULTS: Nonparametric linkage analysis revealed weak linkage evidence on chromosome 7, and association analysis identified SNP tsc0515272 on chromosome 3 as significantly associated with alcoholism. CONCLUSION: Linkage analysis may require large sample sizes and high quality genotyping and marker maps to adequately improve power, while association analysis could hold more promise in efforts to identify variants responsible for complex traits

Physical activity and pre-diabetes—an unacknowledged mid-life crisis: findings from NHANES 2003–2006

The prevalence of pre-diabetes (PD) among US adults has increased substantially over the past two decades. By current estimates, over 34% of US adults fall in the PD category, 84% of whom meet the American Diabetes Association’s criteria for impaired fasting glucose (IFG). Low physical activity (PA) and/or sedentary behavior are key drivers of hyperglycemia. We examined the relationship between PD and objectively measured PA in NHANES 2003–2006 of 20,470 individuals, including 7,501 individuals between 20 and 65 yrs.We excluded all participants without IFG measures or adequate accelerometry data (final N = 1,317). Participants were identified as PD if FPG was 100–125 mg/dL (5.6–6.9 mmol/L). Moderate and vigorous PA in minutes/day individuals were summed to create the exposure variable “moderate-vigorous PA” (MVPA). The analysis sample included 884 normoglycemic persons and 433 with PD. There were significantly fewer PD subjects in the middle (30.3%) and highest (24.6%) tertiles of PA compared to the lowest tertile (35.5%). After adjusting for BMI, participants were 0.77 times as likely to be PD if they were in the highest tertile compared to the lowest PA tertile (p < 0.001). However, these results were no longer significant when age and BMI were held constant. Univariate analysis revealed that physical activity was associated with decreased fasting glucose of 0.5 mg/dL per minute of MVPA, but multivariate analysis adjusting for age and BMI was not significant. Overall, our data suggest a negative association between measures of PA and the prevalence of PD in middle-aged US adults independent of adiposity, but with significant confounding influence from measures of BMI and age

Potential Deaths Averted and Serious Adverse Events Incurred From Adoption of the SPRINT (Systolic Blood Pressure Intervention Trial) Intensive Blood Pressure Regimen in the United States: Projections From NHANES (National Health and Nutrition Examination Survey)

BACKGROUND: SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated a 27% reduction in all-cause mortality with a systolic blood pressure (SBP) goal ofmellitus, stroke, or heart failure. To quantify the potential benefits and risks of SPRINT intensive goal implementation, we estimated the deaths prevented and excess serious adverse events incurred if the SPRINT intensive SBP treatment goal were implemented in all eligible US adults. METHODS: SPRINT eligibility criteria were applied to the 1999 to 2006 National Health and Nutrition Examination Survey and linked with the National Death Index through December 2011. SPRINT eligibility included age ≥50 years, SBP of 130 to 180 mm Hg (depending on the number of antihypertensive medications being taken), and high cardiovascular disease risk. Exclusion criteria were diabetes mellitus, history of stroke, \u3e1 g proteinuria, heart failure, estimated glomerular filtration ratemL·min RESULTS: The mean age was 68.6 years, and 83.2% and 7.4% were non-Hispanic white and non-Hispanic black, respectively. The annual mortality rate was 2.20% (95% confidence interval [CI], 1.91-2.48), and intensive SBP treatment was projected to prevent ≈107 500 deaths per year (95% CI, 93 300-121 200) and give rise to 56 100 (95% CI, 50 800-61 400) episodes of hypotension, 34 400 (95% CI, 31 200-37 600) episodes of syncope, 43 400 (95% CI, 39 400-47 500) serious electrolyte disorders, and 88 700 (95% CI, 80 400-97 000) cases of acute kidney injury per year. The analysis-of-extremes approach indicated that the range of estimated lower- and upper-bound number of deaths prevented per year with intensive SBP control was 34 600 to 179 600. Intensive SBP control was projected to prevent 46 100 (95% CI, 41 800-50 400) cases of heart failure annually. CONCLUSIONS: If fully implemented in eligible US adults, intensive SBP treatment could prevent ≈107 500 deaths per year. A consequence of this treatment strategy, however, could be an increase in serious adverse events

Independent association of resting energy expenditure with blood pressure: confirmation in populations of the African diaspora

Background: Obesity is a major risk factor for hypertension, however, the physiologic mechanisms linking increased adiposity to elevations in blood pressure are not well described. An increase in resting energy expenditure (REE) is an obligatory consequence of obesity. Previous survey research has demonstrated that REE is an independent predictor of blood pressure, and eliminates the co-linear association of body mass index. This observation has received little attention and there have been no attempts to provide a causal explanation. Methods: At baseline in an international comparative study on obesity, 289 participants aged 25–44 were recruited from communities in the US, the Seychelles, Ghana and South Africa and had REE measured with indirect calorimetry. All participants were thought to be free of major illness. Results: In multivariate regression models, both systolic and diastolic blood pressure were positively associated with REE (p < 0.01), while body mass index and fat mass were negatively correlated with systolic blood pressure (p < 0.01, and p < 0.05 respectively), but not diastolic blood pressure. Conclusions: These data confirm previous reports and suggest that a common physiologic abnormality links REE and blood pressure. Elevated catecholamines, a putative metabolic characteristic of obesity, is a possible candidate to explain this association. The direct role of excess adipose tissue is open to question

A comparison of indices of glucose metabolism in five black populations: data from modeling the epidemiologic transition study (METS)

Background: Globally, Africans and African Americans experience a disproportionate burden of type 2 diabetes, compared to other race and ethnic groups. The aim of the study was to examine the association of plasma glucose with indices of glucose metabolism in young adults of African origin from 5 different countries. Methods: We identified participants from the Modeling the Epidemiologic Transition Study, an international study of weight change and cardiovascular disease (CVD) risk in five populations of African origin: USA (US), Jamaica, Ghana, South Africa, and Seychelles. For the current study, we included 667 participants (34.8 ± 6.3 years), with measures of plasma glucose, insulin, leptin, and adiponectin, as well as moderate and vigorous physical activity (MVPA, minutes/day [min/day]), daily sedentary time (min/day), anthropometrics, and body composition. Results: Among the 282 men, body mass index (BMI) ranged from 22.1 to 29.6 kg/m2 in men and from 25.8 to 34.8 kg/m2 in 385 women. MVPA ranged from 26.2 to 47.1 min/day in men, and from 14.3 to 27.3 min/day in women and correlated with adiposity (BMI, waist size, and % body fat) only among US males after controlling for age. Plasma glucose ranged from 4.6 ± 0.8 mmol/L in the South African men to 5.8 mmol/L US men, while the overall prevalence for diabetes was very low, except in the US men and women (6.7 and 12 %, respectively). Using multivariate linear regression, glucose was associated with BMI, age, sex, smoking hypertension, daily sedentary time but not daily MVPA. Conclusion: Obesity, metabolic risk, and other potential determinants vary significantly between populations at differing stages of the epidemiologic transition, requiring tailored public health policies to address local population characteristics

A mixed ecologic-cohort comparison of physical activity & weight among young adults from five populations of African origin

Abstract Background Examination of patterns and intensity of physical activity (PA) across cultures where obesity prevalence varies widely provides insight into one aspect of the ongoing epidemiologic transition. The primary hypothesis being addressed is whether low levels of PA are associated with excess weight and adiposity. Methods We recruited young adults from five countries (500 per country, 2500 total, ages 25–45 years), spanning the range of obesity prevalence. Men and women were recruited from a suburb of Chicago, Illinois, USA; urban Jamaica; rural Ghana; peri-urban South Africa; and the Seychelles. PA was measured using accelerometry and expressed as minutes per day of moderate-to-vigorous activity or sedentary behavior. Results Obesity (BMI ≥ 30) prevalence ranged from 1.4% (Ghanaian men) to 63.8% (US women). South African men were the most active, followed by Ghanaian men. Relatively small differences were observed across sites among women; however, women in Ghana accumulated the most activity. Within site-gender sub-groups, the correlation of activity with BMI and other measures of adiposity was inconsistent; the combined correlation across sites was -0.17 for men and -0.11 for women. In the ecological analysis time spent in moderate-to-vigorous activity was inversely associated with BMI (r = -0.71). Conclusion These analyses suggest that persons with greater adiposity tend to engage in less PA, although the associations are weak and the direction of causality cannot be inferred because measurements are cross-sectional. Longitudinal data will be required to elucidate direction of association

Cardiovascular risk status of Afro-origin populations across the spectrum of economic development: findings from the Modeling the Epidemiologic Transition Study

Background: Cardiovascular risk factors are increasing in most developing countries. To date, however, very little standardized data has been collected on the primary risk factors across the spectrum of economic development. Data are particularly sparse from Africa. Methods: In the Modeling the Epidemiologic Transition Study (METS) we examined population-based samples of men and women, ages 25–45 of African ancestry in metropolitan Chicago, Kingston, Jamaica, rural Ghana, Cape Town, South Africa, and the Seychelles. Key measures of cardiovascular disease risk are described. Results: The risk factor profile varied widely in both total summary estimates of cardiovascular risk and in the magnitude of component factors. Hypertension ranged from 7% in women from Ghana to 35% in US men. Total cholesterol was well under 200 mg/dl for all groups, with a mean of 155 mg/dl among men in Ghana, South Africa and Jamaica. Among women total cholesterol values varied relatively little by country, following between 160 and 178 mg/dl for all 5 groups. Levels of HDL-C were virtually identical in men and women from all study sites. Obesity ranged from 64% among women in the US to 2% among Ghanaian men, with a roughly corresponding trend in diabetes. Based on the Framingham risk score a clear trend toward higher total risk in association with socioeconomic development was observed among men, while among women there was considerable overlap, with the US participants having only a modestly higher risk score. Conclusions: These data provide a comprehensive estimate of cardiovascular risk across a range of countries at differing stages of social and economic development and demonstrate the heterogeneity in the character and degree of emerging cardiovascular risk. Severe hypercholesterolemia, as characteristic in the US and much of Western Europe at the onset of the coronary epidemic, is unlikely to be a feature of the cardiovascular risk profile in these countries in the foreseeable future, suggesting that stroke may remain the dominant cardiovascular event

Accelerometer-measured physical activity is not associated with two-year weight change in African-origin adults from five diverse populations.

BACKGROUND: Increasing population-levels of physical activity (PA) is a controversial strategy for managing the obesity epidemic, given the conflicting evidence for weight loss from PA alone per se. We measured PA and weight change in a three-year prospective cohort study in young adults from five countries (Ghana, South Africa, Jamaica, Seychelles and USA). METHODS: A total of 1,944 men and women had baseline data, and at least 1 follow-up examination including measures of anthropometry (weight/BMI), and objective PA (accelerometer, 7-day) following the three-year study period. PA was explored as 1-minute bouts of moderate and vigorous PA (MVPA) as well as daily sedentary time. RESULTS: At baseline; Ghanaian and South African men had the lowest body weights (63.4 ± 9.5, 64.9 ± 11.8 kg, respectively) and men and women from the USA the highest (93.6 ± 25.9, 91.7 ± 23.4 kg, respectively). Prevalence of normal weight ranged from 85% in Ghanaian men to 29% in USA men and 52% in Ghanaian women to 15% in USA women. Over the two-year follow-up period, USA men and Jamaican women experienced the smallest yearly weight change rate (0.1 ± 3.3 kg/yr; -0.03 ± 3.0 kg/yr, respectively), compared to South African men and Ghanaian women greatest yearly change (0.6.0 ± 3.0 kg/yr; 1.22 ± 2.6 kg/yr, respectively). Mean yearly weight gain tended to be larger among normal weight participants at baseline than overweight/obese at baseline. Neither baseline MVPA nor sedentary time were associated with weight gain. Using multiple linear regression, only baseline weight, age and gender were significantly associated with weight gain. DISCUSSION: From our study it is not evident that higher volumes of PA alone are protective against future weight gain, and by deduction our data suggest that other environmental factors such as the food environment may have a more critical role