Myocardial infarction in the Wisconsin Longitudinal Study: The interaction among environmental, health, social, behavioural and genetic factors

Objectives This study examined how environmental, health, social, behavioural and genetic factors interact to contribute to myocardial infarction (MI) risk. Design Survey data collected by Wisconsin Longitudinal Study (WLS), USA, from 1957 to 2011, including 235 environmental, health, social and behavioural factors, and 77 single- nucleotide polymorphisms were analysed for association with MI. To identify associations with MI we utilized recursive partitioning and random forest prior to logistic regression and chi-squared analyses. Participants 6198 WLS participants (2938 men; 3260 women) who (1) had a MI before 72 years and (2) had a MI between 65 and 72 years. ResultsIn men, stroke (LR OR: 5.01, 95% CI 3.36 to 7.48), high cholesterol (3.29, 2.59 to 4.18), diabetes (3.24, 2.53 to 4.15) and high blood pressure (2.39, 1.92 to 2.96) were significantly associated with MI up to 72 years of age. For those with high cholesterol, the interaction of smoking and lower alcohol consumption increased prevalence from 23% to 41%, with exposure to dangerous working conditions, a factor not previously linked with MI, further increasing prevalence to 50%. Conversely, MI was reported in Conclusions Together these results indicate important differences in factors associated with MI between the sexes, that combinations of factors greatly influence the likelihood of MI, that MI-associated factors change and associations weaken after 65 years of age in both sexes, and that the limited genotypes assessed were secondary to environmental, health, social and behavioral factors

Personality Predicts Mortality Risk: An Integrative Data Analysis of 15 International Longitudinal Studies

This study examined the Big Five personality traits as predictors of mortality risk, and smoking as a mediator of that association. Replication was built into the fabric of our design: we used a Coordinated Analysis with 15 international datasets, representing 44,094 participants. We found that high neuroticism and low conscientiousness, extraversion, and agreeableness were consistent predictors of mortality across studies. Smoking had a small mediating effect for neuroticism. Country and baseline age explained variation in effects: studies with older baseline age showed a pattern of protective effects (HR<1.00) for openness, and U.S. studies showed a pattern of protective effects for extraversion. This study demonstrated coordinated analysis as a powerful approach to enhance replicability and reproducibility, especially for aging-related longitudinal research.Funding support for this project was provided by the National Institute on Aging: P01-AG043362 (Integrative Analysis of Longitudinal Studies of Aging (IALSA), [Scott M. Hofer (PI)]), and Daniel K. Mroczek (CoInvestigator and Project Leader of the IALSA Personality & Health Project, as well as R01-AG018436 [Personality & Well-Being Trajectories in Adulthood, Daniel K. Mroczek, PI])

Genetic diversity fuels gene discovery for tobacco and alcohol use

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe

by the William Vilas Estate Trust, and by the Graduate School of the University of Wisconsin-Madison. We thank Melvin Kohn and Carmi Schooler for helpful comments. The opinions expressed herein are those of the authors.

In an influential body of work extending across more than three decades and drawing o

The relationship between emergency department use and cost-related medication nonadherence among Medicare beneficiaries

OBJECTIVE: The objective of this study was to evaluate the relationship between self reported cost-related nonadherence to medications and emergency department utilization among a population of Medicare beneficiaries. We hypothesized that persons who reported cost-related medication nonadherence (CRN) would have higher emergency department (ED) use. METHODS: We conducted a retrospective cohort study of continuously enrolled Medicare beneficiaries from in 2006 and 2007. We used multivariate logistic regression to evaluate the relationship between ED use and CRN. Our principal dependent variable was any emergency department visit within a 364-day period after the initial interview assessing CRN. Our principal independent variables were two variables to denote CRN: mild CRN, defined as a reduction in medication dose or delay in getting medications because of cost, and severe CRN, defined as a medication not being filled at all due to cost. RESULTS: Our sample consisted of 7177 Medicare Cost Beneficiary Survey (MCBS) MCBS respondents. Approximately 7.5 percent of these respondents reported mild CRN only (n=541) and another 8.2 percent reported severe CRN (n=581). Disabled Medicare beneficiaries with severe CRN were more likely to have at least one ED visit (1.53, 95% CI 1.03–2.26) as compared to both disabled Medicare beneficiaries without CRN and elderly Medicare beneficiaries in all CRN categories. CONCLUSIONS: Our results show an association between severe CRN and emergency department use. Disabled beneficiaries under age 65 who report severe CRN were more likely to have at least one emergency department visit, even when adjusting for other factors that impact utilization

Assessing Health and Health Care in the District of Columbia

This document describes interim findings from a study of health and the health care service delivery system in the District of Columbia. The goals of the study are to: (1) conduct a comprehensive health needs assessment for Washington DC; (2) assess the quality and accessibility of the District\u27s health care delivery system for individuals with urgent or emergent medical needs; and (3) use information from those assessments to identify and assess various policy options for improving the health care delivery system. This document summarizes findings related to the first two goals. A final report will include findings relevant to goal (3)

Assessing Health and Health Care in the District of Columbia: Phase 2 Report

This document describes findings and recommendations from a study of health and the health care service delivery system in the District of Columbia. The goals of the study are to: (1) conduct a comprehensive health needs assessment for Washington DC; (2) assess the quality and accessibility of the District\u27s health care delivery system for individuals with urgent or emergent medical needs; and (3) use information from those assessments to identify and assess various policy options for improving the health care delivery system. Specifically, the document recommends how $135 million in funding from the tobacco settlement should be spent to strengthen the District\u27s health care system. An interim report, RAND Working Paper 534, summarizes findings related to the first two goals. This document primarily addresses the third goal