Population-level Approach Research Articles

Advantages of public green spaces in enhancing population health

Since the burden of chronic diseases is rising globally, there is an urgent need to develop population-level approaches to reducing the risk of chronic diseases. Neighborhood environments, where people spend much of their time, are relevant in this context because they can influence residents’ daily behaviors related to health. In particular, public green spaces (PGS) can confer health benefits through facilitating physical activity, contact with nature, and social interaction. PGS may also mitigate socio-economic inequalities in health. However, despite growing evidence, PGS are generally not fully utilized as a resource for physical activity. Thus, there is substantial scope for enhancing population health through increased visits and active use of PGS. This essay argues that PGS are not only health-enhancing but also practical and workable environmental resources to promote population health. We discuss three “advantages” of using PGS as health promotion initiatives: PGS are easier to modify (than are other structural environmental features); PGS can involve programs to help residents initiate physical activity; and PGS are valued by residents. The essay concludes with a discussion of future research topics, the result of which can be used to convince and assist local authorities and other key stakeholders to use PGS as readily available resources for health promotion.

The Use of the Fluidigm C1 for RNA Expression Analyses of Single Cells.

Understanding the transcriptional heterogeneity that occurs on the level of a single cell is critical to understanding the gene-regulatory mechanisms underlying development and disease. Population-level whole-transcriptome profiling approaches average gene expression across thousands to millions of cells and are unable to delineate the transcriptional signature of individual cells. Considerable biological heterogeneity between individual cells arises from differences in cell lineage, environment, or response to stimulus. The development of single-cell RNA sequencing (RNA-seq) enabled a high-resolution and unbiased analysis of cell transcriptomes. This unit describes a procedure utilizing an automated microfluidic platform, the Fluidigm C1 system, to simultaneously isolate dozens of single cells in a size- and shape-dependent manner. The microfluidic platform processes cells in individual nanoliter-scale reactions to convert their contents into double-stranded cDNA. This cDNA is used to make dual-indexed libraries using the Illumina Nextera XT library preparation kit for eventual RNA-seq analysis. © 2018 by John Wiley & Sons, Inc.

A National Research Agenda for the Transition of Youth With Autism.

In this article, we outline a national research agenda to improve the transition to adulthood among youth with autism. We synthesized the results from 5 interconnected sets of activities: (1) a scoping review of published autism research and research priority statements, (2) a series of key informant interviews with stakeholders, (3) a 2-day National Research Agenda meeting, (4) a modified Delphi survey of stakeholders, and (5) 2 formal reviews of published literature on autism and transition. We identified 2 overarching priorities to advance research about autism and transition: (1) increased focus on community- and systems-level factors that influence outcomes with population-level approaches to measuring outcomes and (2) greater involvement of people with autism in establishing research priorities, designing research studies, and producing study findings and recommendations. We discuss how the life course framework can guide future inquiry that addresses gaps in extant research.

Exploring the Potential Campus-Level Impact of Online Universal Sexual Assault Prevention Education.

Campus sexual assault is a long-standing challenge and continues to be a severe problem for American higher education. The present study examines the short-term impact of a widely utilized sexual violence prevention course for matriculating college students as a population-level prevention approach. The course focuses on correcting misperceptions of normative behavior, increasing students’ likelihood to intervene in disconcerting situations, and encouraging empathy and support for victims. Participants were 167,424 first-year college students from 80 four-year institutions who completed preintervention and postintervention surveys to assess changes in composite factor scores derived from 20 attitudinal, self-efficacy, and behavioral intention items. Employing the composite factor scores as dependent variables, individual ANOVAs were run for each of the institutions to test whether there were significant increases in mean factor scores. High percentages of institutions saw statistically significant increases (p < .05) in self-reported ability and intention to intervene to prevent sexual assault and relationship violence (98%), empathy and support for victims (84%), and corrected perceptions of social norms (75%). Fewer schools saw significant reductions in endorsement of sexual assault myths (34%). These findings suggest that when implemented as a population-level intervention for all first-year college students, the prevention course can foster accurate perceptions of positive social norms, increase empathy and support for victims, and increase students’ stated ability and intention to intervene.

Obesity Progression Between Young Adulthood and Midlife and Incident Diabetes: A Retrospective Cohort Study of U.S. Adults.

Understanding how changes in weight over the life course shape risk for diabetes is critical for the prevention of diabetes. Using data from the National Health and Nutrition Examination Survey (NHANES), we investigated the association between self-reported weight change from young adulthood to midlife and incident diabetes. We categorized individuals into four weight-change groups: those who remained nonobese (stable nonobese), those who moved from an obese BMI to a nonobese BMI (losing), those who moved from a nonobese BMI to an obese BMI (gaining), and those who remained obese (stable obese). Diabetes status was determined by self-report of a prior diagnosis, and age at diagnosis was used to establish time of diabetes onset. Hazard ratios (HRs) relating weight change to incident diabetes over 10 years of follow-up were calculated using Cox models adjusting for covariates. Those who were obese and lost weight exhibited a significantly lower risk (HR 0.33; 95% CI 0.14, 0.76) of diabetes compared with those with stable obesity. We also observed lower risk among those who were stable nonobese (HR 0.22; 95% CI 0.18, 0.28) and those in the gaining category (HR 0.70; 95% CI 0.57, 0.87). Further, there was evidence of an increased incidence of diabetes among obese individuals who lost weight compared with individuals who were stable nonobese; however, weight loss was rare, and the association was not statistically significant. If those who were obese had become nonobese during the 10-year period, we estimate that 9.1% (95% CI 5.3, 12.8) of observed diabetes cases could have been averted, and if the population had maintained a normal BMI during the period, 64.2% (95% CI 59.4, 68.3) of cases could have been averted. The findings from this study underscore the importance of population-level approaches to the prevention and treatment of obesity across the life course of individuals.

Five Community-wide Approaches to Physical Activity Promotion: A Cluster Analysis of These Activities in Local Health Jurisdictions in 6 States.

Local health departments (LHDs) have essential roles to play in ensuring the promotion of physical activity (PA) in their communities in order to reduce obesity. Little research exists, however, regarding the existence of these PA interventions across communities and how these interventions may impact community health. In this exploratory study, we used cluster analysis to identify the structure of co-occurring PA interventions, followed by regression analysis to quantify the association between the patterns of PA interventions and prevalence of PA and obesity at a population level. Our study setting included local health jurisdictions in Colorado, Florida, Minnesota, New Jersey, Tennessee, and Washington. Participating jurisdictions were those 218 local health jurisdictions (mostly counties) from which LHD leaders had provided data in 2013 for the Multi-Network Practice and Outcome Variation Examination Study. We obtained unique public health activities data on PA interventions conducted in 2012 from 218 LHDs in 6 participating states. We categorized jurisdictions using cluster analysis, based on PA intervention approaches indicated by LHD leaders as available in their communities and then examined associations between categories and prevalence of obesity and of residents engaged in PA. We identified 5 distinct PA intervention categories representing community-wide approaches-Comprehensive Approach, Built Environment, Personal Health, School-Based Interventions, and No Apparent Activities. Prevalence rates of obesity and PA among jurisdictions in the intervention clusters were significantly different from jurisdictions with No Apparent Activities, with more population-level approaches most significantly related to beneficial outcomes. Our findings suggest the importance of standardized public health services data for generating evidence regarding health-related outcomes. The intervention categories we identified appear to reflect broad, local community-wide prevention approaches and demonstrated that population-level PA interventions can be testable and may have particularly beneficial relationships to community health. Widespread adoption of such standardized data depicting local public health prevention activity could support monitoring practice change, performance improvement, comparisons across communities that could reduce unnecessary variation, and the generation of evidence for public health practice and policy-making.

A public health needs assessment for domestic indoor overheating.

Indoor overheating is a potentially fatal health hazard that was identified as an issue requiring urgent action in the 2017 UK Climate Change Risk Assessment. We aimed to make research on this issue more accessible to local public health teams to encourage its inclusion in local strategic needs assessments. Epidemiological health needs assessment. We adapted established health needs assessment methods, focussing on the epidemiological component, drawing evidence from a non-systematic literature review that was complemented by discussion with experts. Indoor overheating arises from an interaction between occupants' susceptibility to heat, their behaviour and the building's location and its characteristics. Many of these factors are interrelated and, at a national level, are expected to vary over time with demographic and climate change. Understanding these factors, ways to mitigate them and a long-term view are all essential for managing overheating risk. There is a need for services to be provided at the local level that consider the home environment and its impact on health in all seasons. A population-level approach to risk management across a local area is also useful to inform collaborative efforts to reduce future incidence of overheating and better understand how it varies with socio-economic deprivation.

Neighbourhood typologies and associations with body mass index and obesity: A cross-sectional study

Little research has investigated associations between a combined measure of the food and physical activity (PA) environment, BMI (body-mass-index) and obesity. Cross-sectional data (n=22,889, age 18–86years) from the Yorkshire Health Study were used [2010−2013]. BMI was calculated using self-reported height and weight; obesity=BMI≥30. Neighbourhood was defined as a 2km radial buffer. Food outlets and PA facilities were sourced from Ordnance Survey Points of Interest (PoI) and categorised into ‘fast-food’, ‘large supermarkets’, ‘convenience and other food retail outlets’ and ‘physical activity facilities’. Parks were sourced from Open Street Map. Latent class analysis was conducted on these five environmental variables and availability was defined by quartiles of exposure. Linear and logistic regressions were then conducted for BMI and obesity respectively for different neighbourhood types. Models adjusted for age, gender, ethnicity, area-level deprivation, and rural/urban classification. A five-class solution demonstrated best fit and was interpretable. Neighbourhood typologies were defined as; ‘low availability’, ‘moderate availability’, ‘moderate PA, limited food’, ‘saturated’ and ‘moderate PA, ample food’. Compared to low availability, one typology demonstrated lower BMI (saturated, b=−0.50, [95% CI=−0.76, −0.23]), while three showed higher BMI (moderate availability, b=0.49 [0.27, 0.72]; moderate PA, limited food, b=0.30 [0.01, 0.59]; moderate PA, ample food, b=0.32 [0.08, 0.57]). Furthermore, compared to the low availability, saturated neighbourhoods showed lower odds of obesity (OR=0.86 [0.75, 0.99]) while moderate availability showed greater odds of obesity (OR=1.18 [1.05, 1.32]). This study supports population-level approaches to tackling obesity however neighbourhoods contained features that were health-promoting and -constraining.

Embedding Health Equity Strategically within Healthy Built Environments to Improve Walkability ( breakout presentation )

Background Population health promotion approaches have become increasingly focused in recent years on improving walkability in built environments. Communities, health sectors and public leaders alike have recognized that factors such as transportation networks and neighbourhood design have a significant impact on the physical activity levels and health of populations. Despite this attention on healthy built environments and walkability, health equity is often not an explicit strategic focus. Description of Program Recognizing the need for frameworks to prioritize, integrate, and measure health equity within built environments, Saskatoon Health Region Population and Public Health Services (SHR) has embedded health equity within this work. Aligning population-level approaches, a health equity focus, and the overarching goal of better health for all has positive impacts on walkability and other forms of active transportation through healthy built environments. With partners, SHR carried out a Health Equity Impact Assessment of the City of Saskatoon’s Growth Plan, focussing on the areas of active transportation, public transportation and growth along major corridors. This report highlighted the potential negative impacts that can be mitigated as well as the positive impacts that can be enhanced by incorporating health equity into the planning process. Outcomes Walkability, and active transportation overall, has many benefits, including improved health. It also can be a catalyst for building social capital, supporting economic development and providing economical means of supporting people of all income levels to move around their communities. Implications In order to foster better health for all, health equity must be at the forefront within a health promotion strategy, working in partnership with municipal governments and other partners. Deliberate and explicit planning is needed in order to integrate health equity into walkability and how communities are planned and built. Public Health can act as a partner in the work alongside municipalities, to help bring this perspective to facilitate physical and social environments for all to thrive.

Using a chronic hepatitis B Registry to support population-level liver cancer prevention in Sydney, Australia.

BackgroundApproximately 1% of Australians have chronic hepatitis B (CHB), which disproportionately affects people born in hepatitis B-endemic countries. Currently, approximately half of the people affected remain undiagnosed and antiviral treatment uptake is suboptimal (~5%). This increases the likelihood of developing end-stage disease complications, particularly hepatocellular cancer (HCC), and largely accounts for the significant increases in HCC incidence and mortality in Australia over the last decades. As our previous economic modeling suggested that CHB screening and treatment is cost-effective, we tested the feasibility of a primary care-based model of CHB diagnosis and management to prevent HCC.Materials and methodsFrom 2009 to 2016, the B Positive program trialed a CHB screening and management program in an area of high disease prevalence in Sydney, Australia. Trained local primary care providers (general practitioners) screened and managed their CHB patients using a purpose-built CHB Registry and a risk stratification algorithm, which allocated patients to ongoing primary care-based management or specialist referral.ResultsThe program enrolled and followed up >1,500 people (25% of the target population). Their median age was 48 years, with most participants being born in China (50%) or Vietnam (32%). The risk stratification algorithm allocated most Registry participants (n=847 or 79%) to primary care-based management, reducing unnecessary specialist referrals. The level of antiviral treatment uptake in Registry patients was 18%, which was the optimal level in this population group.ConclusionThis pilot program demonstrated that primary care-based hepatitis B diagnosis and management is acceptable to patients and their care providers and significantly increases compliance with treatment guidelines. This would suggest that scaling up access to hepatitis B treatment is achievable and can provide a means to operationalize a population-level approach to CHB management and liver cancer prevention.

SaccharomycesIDentifier, SID: strain-level analysis of Saccharomyces cerevisiae populations by using microsatellite meta-patterns

Saccharomyces cerevisiae is a common yeast with several applications, among which the most ancient is winemaking. Because individuals belonging to this species show a wide genetic and phenotypic variability, the possibility to identify the strains driving fermentation is pivotal when aiming at stable and palatable products. Metagenomic sequencing is increasingly used to decipher the fungal populations present in complex samples such as musts. However, it does not provide information at the strain level. Microsatellites are commonly used to describe the genotype of single strains. Here we developed a population-level microsatellite profiling approach, SID (Saccharomyces cerevisiae IDentifier), to identify the strains present in complex environmental samples. We optimized and assessed the performances of the analytical procedure on patterns generated in silico by computationally pooling Saccharomyces cerevisiae microsatellite profiles, and on samples obtained by pooling DNA of different strains, proving its ability to characterize real samples of grape wine fermentations. SID showed clear differences among S. cerevisiae populations in grape fermentation samples, identifying strains that are likely composing the populations and highlighting the impact of the inoculation of selected exogenous strains on natural strains. This tool can be successfully exploited to identify S. cerevisiae strains in any kind of complex samples.

A prospectus for ethical analysis of ageing individuals' responsibility to prevent cognitive decline.

As the world's population ages, governments and non-governmental organizations in developed countries are promoting healthy cognitive ageing to reduce the rate of age-related cognitive decline and sustain economic productivity in an ageing workforce. Recommendations from the Productivity Commission (Australia), Dementia Australia, Government Office for Science (UK), Presidential Commission for the Study of Bioethical Issues (USA), Institute of Medicine (USA), among others, are encouraging older adults to engage in mental, physical, and social activities. These lifestyle recommendations for healthy cognitive ageing are timely and well supported by scientific evidence but they make implicit normative judgments about the responsibility of ageing individuals to prevent cognitive decline. Ethical tensions arise when this individual responsibility collides with social and personal realities of ageing populations. First, we contextualize the priority given to healthy cognitive ageing within the current brain-based medical and social discourses. Second, we explore the individual responsibility by examining the economic considerations, medical evidence and individual interests that relate to the priority given to healthy cognitive ageing. Third, we identify three key ethical challenges for policymakers seeking to implement lifestyle recommendations as an effective population-level approach to healthy cognitive ageing. The result is a prospectus for future in-depth analysis of ethical tensions that arise from current policy discussions of healthy cognitive ageing.

Current threats faced by Neotropical parrot populations

Psittaciformes (parrots, cockatoos) are among the most endangered birds, with 31% of Neotropical species under threat. The drivers of this situation appear to be manifold and mainly of anthropogenic origin. However, this assessment is based on the last extensive consultation about the conservation situation of parrots carried out in the 1990s. Given the rapid development of anthropogenic threats, updated data are needed to strategize conservation actions. Using a population approach, we addressed this need through a wide-ranging consultation involving biologists, wildlife managers, government agencies and non-governmental conservation organizations. We gathered up-to-date information on threats affecting 192 populations of 96 Neotropical parrot species across 21 countries. Moreover, we investigated associations among current threats and population trends. Many populations were affected by multiple threats. Agriculture, Capture for the Pet Trade, Logging, each of them affected >55% of the populations, suggesting a higher degree of risk than previously thought. In contrast to previous studies at the species level, our study showed that the threat most closely associated with decreasing population trends is now Capture for the local Pet Trade. Other threats associated with decreasing populations include Small-holder Farming, Rural Population Pressure, Nest Destruction by Poachers, Agro-industry Grazing, Small-holder Grazing, and Capture for the international Pet Trade. Conservation actions have been implemented on <20% of populations. Our results highlight the importance of a population-level approach in revealing the extent of threats to wild populations. It is critical to increase the scope of conservation actions to reduce the capture of wild parrots for pets.

Trends in Prehypertension and Hypertension Risk Factors in US Adults: 1999-2012.

Prehypertension is associated with increased risk for hypertension and cardiovascular disease. Data are limited on the temporal changes in the prevalence of prehypertension and risk factors for hypertension and cardiovascular disease among US adults with prehypertension. We analyzed data from 30 958 US adults ≥20 years of age who participated in the National Health and Nutrition Examination Surveys between 1999 and 2012. Using the mean of 3 blood pressure (BP) measurements from a study examination, prehypertension was defined as systolic BP of 120 to 139 mm Hg and diastolic BP <90 mm Hg or diastolic BP of 80 to 89 mm Hg and systolic BP <140 mm Hg among participants not taking antihypertensive medication. Between 1999-2000 and 2011-2012, the percentage of US adults with prehypertension decreased from 31.2% to 28.2% (P trend=0.007). During this time period, the prevalence of several risk factors for cardiovascular disease and incident hypertension increased among US adults with prehypertension, including prediabetes (9.6% to 21.6%), diabetes mellitus (6.0% to 8.5%), overweight (33.5% to 37.3%), and obesity (30.6% to 35.2%). There was a nonstatistically significant increase in no weekly leisure-time physical activity (40.0% to 43.9%). Also, the prevalence of adhering to the Dietary Approaches to Stop Hypertension eating pattern decreased (18.4% to 11.9%). In contrast, there was a nonstatistically significant decline in current smoking (25.9% to 23.2%). In conclusion, the prevalence of prehypertension has decreased modestly since 1999-2000. Population-level approaches directed at adults with prehypertension are needed to improve risk factors to prevent hypertension and cardiovascular disease.

An investigation of emotion dynamics in major depressive disorder patients and healthy persons using sparse longitudinal networks.

BackgroundDifferences in within-person emotion dynamics may be an important source of heterogeneity in depression. To investigate these dynamics, researchers have previously combined multilevel regression analyses with network representations. However, sparse network methods, specifically developed for longitudinal network analyses, have not been applied. Therefore, this study used this approach to investigate population-level and individual-level emotion dynamics in healthy and depressed persons and compared this method with the multilevel approach.MethodsTime-series data were collected in pair-matched healthy persons and major depressive disorder (MDD) patients (n = 54). Seven positive affect (PA) and seven negative affect (NA) items were administered electronically at 90 times (30 days; thrice per day). The population-level (healthy vs. MDD) and individual-level time series were analyzed using a sparse longitudinal network model based on vector autoregression. The population-level model was also estimated with a multilevel approach. Effects of different preprocessing steps were evaluated as well. The characteristics of the longitudinal networks were investigated to gain insight into the emotion dynamics.ResultsIn the population-level networks, longitudinal network connectivity was strongest in the healthy group, with nodes showing more and stronger longitudinal associations with each other. Individually estimated networks varied strongly across individuals. Individual variations in network connectivity were unrelated to baseline characteristics (depression status, neuroticism, severity). A multilevel approach applied to the same data showed higher connectivity in the MDD group, which seemed partly related to the preprocessing approach.ConclusionsThe sparse network approach can be useful for the estimation of networks with multiple nodes, where overparameterization is an issue, and for individual-level networks. However, its current inability to model random effects makes it less useful as a population-level approach in case of large heterogeneity. Different preprocessing strategies appeared to strongly influence the results, complicating inferences about network density.

Public knowledge and understanding of dementia-evidence from a national survey in Ireland.

there is growing consensus around the importance of population level approaches which seek to improve public knowledge and awareness of dementia. to assess knowledge of the relationship between dementia and ageing, and of the risk and protective factors associated with it, among the general public in Ireland. cross-sectional survey. Participants selected using quota sampling based on Census data. the final sample of 1,217 respondents provided estimates of dementia knowledge in the Irish population. Logistic regression was used to assess the impact of potential predictor variables on knowledge of dementia. a majority (52%) reported that they knew someone living with dementia. Just 39% were confident that they could tell the difference between the early signs of dementia and normal ageing. Less than half (46%) believed that there were things they could do to reduce their risk of developing dementia, and knowledge of risk and protective factors for dementia was very poor. Although significant differences were seen according to area of residence, social class and experience of dementia, even those groups with 'better' understanding demonstrated substantial knowledge deficits regarding risk and protective factors. the general public in Ireland are confused about the relationship between dementia and ageing, and knowledge of risk and protective factors for dementia is very poor. While not dissimilar to those reported internationally, the findings present a challenge to those tasked with promoting behaviour change and interventions to delay or prevent the onset of dementia.

Advances in single-cell RNA sequencing and its applications in cancer research.

Unlike population-level approaches, single-cell RNA sequencing enables transcriptomic analysis of an individual cell. Through the combination of high-throughput sequencing and bioinformatic tools, single-cell RNA-seq can detect more than 10,000 transcripts in one cell to distinguish cell subsets and dynamic cellular changes. After several years’ development, single-cell RNA-seq can now achieve massively parallel, full-length mRNA sequencing as well as in situ sequencing and even has potential for multi-omic detection. One appealing area of single-cell RNA-seq is cancer research, and it is regarded as a promising way to enhance prognosis and provide more precise target therapy by identifying druggable subclones. Indeed, progresses have been made regarding solid tumor analysis to reveal intratumoral heterogeneity, correlations between signaling pathways, stemness, drug resistance, and tumor architecture shaping the microenvironment. Furthermore, through investigation into circulating tumor cells, many genes have been shown to promote a propensity toward stemness and the epithelial-mesenchymal transition, to enhance anchoring and adhesion, and to be involved in mechanisms of anoikis resistance and drug resistance. This review focuses on advances and progresses of single-cell RNA-seq with regard to the following aspects:1. Methodologies of single-cell RNA-seq2. Single-cell isolation techniques3. Single-cell RNA-seq in solid tumor research4. Single-cell RNA-seq in circulating tumor cell research5. Perspectives

Alcohol Brief Interventions (ABIs) for male remand prisoners: protocol for development of a complex intervention and feasibility study (PRISM-A)

IntroductionIn the UK, a significant proportion of male remand prisoners have alcohol problems. Alcohol Brief Interventions (ABIs) are an effective component of a population-level approach to harmful and hazardous drinking....

A new bio-inspired, population-level approach to the socioeconomic evolution of dynamic spectrum access services

Evolutionary species and quasispecies models provide the universal and flexible basis for a large-scale description of the dynamics of evolutionary systems, which can be built conceived as a constraint satisfaction dynamics. It represents a general framework to design and study many novel, technologically contemporary models and their variants. Here, we apply the classical quasispecies concept to model the emerging dynamic spectrum access (DSA) markets. The theory describes the mechanisms of mimetic transfer, competitive interactions between socioeconomic strata of the end-users, their perception of the utility and inter-operator switching in the variable technological environments of the operators offering the wireless spectrum services. The algorithmization and numerical modeling demonstrate the long-term evolutionary socioeconomic changes which reflect the end-user preferences and results of the majorization of their irrational decisions in the same manner as the prevailing tendencies which are embodied in the efficient market hypothesis.

Abstract P094: Genetic Risk, Incident Coronary Heart Disease Events, and the Benefits of a Healthy Lifestyle: Joint and Interacting Effects Across Four US Cohorts

Background: Recent GWAS revealed single nucleotide polymorphisms (SNPs) that cumulatively increase risk of CHD in those of European ancestry. We quantified the magnitude of preventive effects of healthy lifestyle against the countervailing effects of genetic risk on incident CHD, and assessed potential interactions. Methods: We extracted SNPs of genome-wide significance (&lt;5 x 10 -8 ) for CHD from CARDIoGRAMplusC4 GWAS, and created a weighted 57-SNP genetic risk score (GRS). Baseline covariates, healthy lifestyle score (including diet pattern, physical activity, smoking and BMI), and incident CHD were harmonized across 4 US cohorts (WHI, ARIC, CHS, and MESA) using dbGaP data. Pooled analyses were run using one-step individual participant data multivariate regressions in Caucasians without prevalent CVD. Results: Among 22,412 adults, the GRS was associated with incident CHD (n = 3001 cases) across each cohort (pooled GRS quintile (Q)5 vs Q1, RR (95% CI): 1.59 (1.41-1.79)), independent of all demographic and lifestyle variables. The lifestyle score was more strongly associated with CHD (pooled Q1 vs Q5, RR: 1.94 (1.71-2.20)) than the GRS, and better discriminated those who had a CHD event ( P =0.025 for difference in AUROC curves). When compared to population-level analysis, joint effects analysis revealed significant heterogeneity within quartiles of lifestyle score on risk of incident CHD ( Table ). Interactions between the GRS and diet pattern ( P =0.022) and trans fats ( P =0.046) were observed. Effects of trans fats on CHD risk appear to be concentrated in those with a higher GRS: for trans fats &gt;2.4% of energy, RRs for increasing GRS quartiles are 0.92 (0.62-1.36), 1.13 (0.79-1.62), 1.43 (1.01-2.01), and 1.84 (1.30-2.61), compared to those in the lowest quartile of trans fat (&lt;1.3% of energy) and lowest GRS quartile. Conclusion: A joint effects approach reveals significant inter-individual variability in lifestyle on CHD risk by underlying genetic risk that is obscured by a conventional population-level effects approach.