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BackgroundThe presence of population structure in a sample may confound the search for important genetic loci associated with disease. Our four samples in the Family Investigation of Nephropathy and Diabetes (FIND), European Americans, Mexican Americans, African Americans, and American Indians are part of a genome- wide association study in which population structure might be particularly important. We therefore decided to study in detail one component of this, individual genetic ancestry (IGA). From SNPs present on the Affymetrix 6.0 Human SNP array, we identified 3 sets of ancestry informative markers (AIMs), each maximized for the information in one the three contrasts among ancestral populations: Europeans (HAPMAP, CEU), Africans (HAPMAP, YRI and LWK), and Native Americans (full heritage Pima Indians). We estimate IGA and present an algorithm for their standard errors, compare IGA to principal components, emphasize the importance of balancing information in the ancestry informative markers (AIMs), and test the association of IGA with diabetic nephropathy in the combined sample.ResultsA fixed parental allele maximum likelihood algorithm was applied to the FIND to estimate IGA in four samples: 869 American Indians; 1385 African Americans; 1451 Mexican Americans; and 826 European Americans. When the information in the AIMs is unbalanced, the estimates are incorrect with large error. Individual genetic admixture is highly correlated with principle components for capturing population structure. It takes ~700 SNPs to reduce the average standard error of individual admixture below 0.01. When the samples are combined, the resulting population structure creates associations between IGA and diabetic nephropathy.ConclusionsThe identified set of AIMs, which include American Indian parental allele frequencies, may be particularly useful for estimating genetic admixture in populations from the Americas. Failure to balance information in maximum likelihood, poly-ancestry models creates biased estimates of individual admixture with large error. This also occurs when estimating IGA using the Bayesian clustering method as implemented in the program STRUCTURE. Odds ratios for the associations of IGA with disease are consistent with what is known about the incidence and prevalence of diabetic nephropathy in these populations.

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.

Although global health is a recommended content area for the future of education in public health, no standardized global health competency model existed for master-level public health students. Without such a competency model, academic institutions are challenged to ensure that students are able to demonstrate the knowledge, skills, and attitudes (KSAs) needed for successful performance in today's global health workforce. The Association of Schools of Public Health (ASPH) sought to address this need by facilitating the development of a global health competency model through a multistage modified-Delphi process. Practitioners and academic global health experts provided leadership and guidance throughout the competency development process. The resulting product, the Global Health Competency Model 1.1, includes seven domains and 36 competencies. The Global Health Competency Model 1.1 provides a platform for engaging educators, students, and global health employers in discussion of the KSAs needed to improve human health on a global scale.

Physicians frequently are early adopters of healthy behaviors based on their knowledge and economic resources. The mortality patterns of physicians in the United States, particularly suicide, have not been rigorously described for over a decade. Previous studies have shown lower all-cause mortality among physicians yet reported conflicting results about cause-specific mortality such as suicide. In this study, we compared all-cause and cause-specific mortality in a sample of physicians to the age-gender matched general U.S. population from 1948 through 1998. We also compared the mortality experience across medical specialities. The risk of all-cause mortality was 56% lower than expected in men, and 26% lower in women, compared to the general population. Standardized mortality ratios (SMRs) were markedly lower for diseases strongly linked to smoking, e.g., cardiovascular diseases, respiratory diseases, and lung cancer. Suicide was the only cause of death where risk was greater than the general population. Overall, we found that physicians are at substantially lower risk of dying compared to the general population for all causes of death except suicide. The findings for suicide are strikingly different than other causes of death and should provide impetus for new research on the mental health of physicians.

Objectives. We used longitudinal data from the Johns Hopkins Precursors Study to test the hypothesis that written propositional density measured early in life is lower for people who develop dementia categorized as Alzheimer's disease (AD). This association was reported in 1996 for the Nun Study, and the Precursors Study offered an unprecedented chance to reexamine it among respondents with different gender, education, and occupation profiles. Methods. Eighteen individuals classified as AD patients (average age at diagnosis: 74) were assigned 2 sex-and-age matched controls, and propositional density in medical school admission essays (average age at writing: 22) was assessed via Computerized Propositional Idea Density Rater 3 linguistic analysis software. Adjusted odds ratios (ORs) for the matched case-control study were calculated using conditional (fixed-effects) logistic regression. Results. Mean propositional density is lower for cases than for controls (4.70 vs. 4.99 propositions per 10 words, 1-sided p = .01). Higher propositional density substantially lowers the odds of AD (OR = 0.16, 95% confidence interval = 0.03-0.90, 1-sided p = .02). Discussion. Propositional density scores in writing samples from early adulthood appear to predict AD in later life for men as well as women. Studies of cognition across the life course might beneficially incorporate propositional density as a potential marker of cognitive reserve. Key Words: AD--Cognitive reserve--Dementia--Propositional density. doi: 10.1093/geronb/gbq064.

Objective: Recall of past alcohol intake is used in many studies of chronic disease, but few studies have been able to examine its long-term reliability. Method: We sought to assess the reliability of recalled alcohol intake assessed at an average age of 70 years in 2001, after 15 and 23 years of follow-up, in a prospective study of medical students in classes 1948 to 1964. Results: Average reported alcohol intake 15 years and 23 years prior were 6.3 and 7.4 drinks per week, respectively. Recall of alcohol intake overestimated the concurrently reported intake after 15 years by a mean of 0.47 (95% CI [0.10, 0.85]) drinks per week and underestimated intake after 23 years by a mean of 0.79 (95% CI [-1.27, -0.30]) drinks per week, mostly driven by differences between concurrently reported and recalled distilled spirits consumption. Characteristics associated with underestimation of alcohol recall were age of 71 years or older in 2001, self-report of memory difficulties, and self-report of difficulties in physical functioning. In multivariate regression analyses combining 15- and 23-year recall, subjects who reported consumption of more than 14 alcoholic drinks per week in 2001 marginally overestimated recall by slightly more than 1 drink per week (M = 1.18 drinks/week, 95% CI [-0.03, 2.40]). Conclusions: Although significant differences were detected, recalled alcohol intake after 15 and 23 years of follow-up is remarkably reliable. (J. Stud. Alcohol Drugs, 71, 143-149, 2010), VALID AND RELIABLE ASSESSMENT of alcohol intake is important in many studies of chronic disease and health behaviors. Studies that characterize past or lifetime alcohol use assume that participants can [...]

The study explored the effect of tobacco smoking on deaths from various causes and estimated the number of deaths attributable to smoking in China. Results show that smoking is a major risk factor for mortality and that a sustained national anti-smoking campaign is needed to reduce smoking-related deaths.

The major causes of death and amendable risk factors were examined in a nationally representative cohort of numerous men and women of 40 years and above in China. Findings suggested that the major causes of death among Chinese adults were vascular disease and cancer, which could be reduced by controlling hypertension, terminating smoking, increasing physical activity, and good food habits.

Inflammation and malnutrition may cause cholesterol levels to decrease, according to a study of 823 dialysis patients. This could explain why dialysis patients with low cholesterol levels have an increased risk of death. It is not because high cholesterol levels are beneficial, it is because low cholesterol levels are a marker for inflammation and malnutrition. For this reason, dialysis patients with high cholesterol levels should take cholesterol-lowering drugs.

Measures of family stability, sociocultural background, and emotional ties to parents in medical students (N = 589, mean age = 22 years) predicted their social support measures, assessed 23 to 39 years later (mean age = 56 years). Father's education and family's involvement in church were positively associated with group participation (number of group memberships), whereas parental loss between the ages of 11 and 20 was negatively associated with group participation; perceived emotional closeness to parents was positively associated with social closeness (number of close contacts providing emotional and instrumental support). Thus, group participation and social closeness were influenced by distinctly different childhood factors.

Diabetes mellitus appears to substantially increase the risk of end-stage renal disease (ESRD). Researchers analyzed the incidence of ESRD in 332,544 men in the Multiple Risk Factor Intervention Trial (MRFIT) between 1975 and 1990. Compared to non-diabetics, diabetics had 92 times the risk of developing ESRD caused by diabetes and also 3 times the risk of ESRD caused by other factors. Their overall risk of ESRD from any cause was 9 times the risk in non-diabetics. Adequate blood glucose control could prevent many of these cases of ESRD., Context.--Diabetes is a frequent cause of end-stage renal disease (ESRD). However, the degree of risk is uncertain. Objective.--To determine the relative risk (RR) of ESRD related to diabetes in the United States. Design.--Nonconcurrent prospective cohort study. Participants.--A total of 332544 men aged 35 to 57 years from 18 US cities screened in 1973 to 1975 for participation in the Multiple Risk Factor Intervention Trial (MRFIT). Main Exposure.--Diabetes mellitus defined by self-reported use of medication for diabetes at baseline. Main Outcome.--Incident ESRD through 1990 assessed from a national ESRD registry and by surveillance for death from renal disease. Results.--Over an average follow-up of 16 years, there were 136 cases of ESRD in 5147 diabetic men and 678 cases in 327 397 nondiabetic men. Age-adjusted incidence of all-cause ESRD in the diabetic men was 199.8 per 100 000 person-years compared with 13.7 per 100 000 person years in their nondiabetic counterparts (RR, 12.7; 95% confidence interval [CI], 10.5-15.4). Diabetic men were also at higher risk for ESRD ascribed to causes other than diabetes (RR=4.3; 95% CI, 3.2-5.9). With simultaneous adjustment for age, ethnicity, income, blood pressure, serum cholesterol level, and history of myocardial infarction, diabetic men remained at higher risk for all-cause ESRD (RR, 9.0; 95% CI, 7.4-11.0), ESRD ascribed to diabetes (RR 92.3; 95% CI, 64.6-131.9), and ESRD ascribed to nondiabetic causes (RR, 3.0 95% CI, 2.2-4.1). Conclusions.--Diabetes mellitus is a strong independent risk factor for ESRD, even for ESRD ascribed to causes other than diabetes. Improvements in the prevention and control of diabetes should produce substantial reductions in ESRD incidence. JAMA. 1997;278:2069-2074

Increasing dietary potassium may lower blood pressure. Researchers used meta-analysis to review 33 clinical trials assessing the health benefits of potassium supplementation in 2,609 patients. Potassium supplementation reduced systolic blood pressure by an average of 3 millimeters of mercury and diastolic blood pressure an average of 2 millimeters of mercury. Potassium supplementation appeared to be especially beneficial in people who could not reduce their sodium intake., Objective. -- To assess the effects of supplementation with oral potassium on blood pressure in humans. Design. -- Meta-analysis of randomized controlled trials. Data Sources. -- English-language articles published before July 1995. Study Selection. -- Thirty-three randomized controlled trials (2609 participants) in which potassium supplementation was the only difference between the intervention and control conditions. Data Extraction. -- Using a standardized protocol, 2 of us independently abstracted information on sample size, duration, study design, potassium dose, participant characteristics, and treatment results. Results. -- By means of a random-effects model, findings from individual trials were pooled, after results for each trial were weighted by the inverse of its variance. An extreme effect of potassium in lowering blood pressure was noted in 1 trial. After exclusion of this trial, potassium supplementation was associated with a significant reduction in mean (95% confidence interval) systolic and diastolic blood pressure of -3.11 mm Hg (-1.91 to -4.31 mm Hg) and -- 1.97 mm Hg (-0.52 to -3.42 mm Hg), respectively. Effects of treatment appeared to be enhanced in studies in which participants were concurrently exposed to a high intake of sodium. Conclusions. -- Our results support the premise that low potassium intake may play an important role in the genesis of high blood pressure. Increased potassium intake should be considered as a recommendation for prevention and treatment of hypertension, especially in those who are unable to reduce their intake of sodium.