Polygenic Risk Moderates the Impact of Greenness on Cardiovascular Health among HCHS/SOL Hispanic/Latinos ABSTRACT Hispanics/Latinos, the largest U.S. minority group, are at relatively high risk for metabolic syndrome (MetS) which is comprised of multiple cardiovascular disease (CVD) risk factors including obesity, high blood pressure, high cholesterol, and high blood glucose. Neighborhood greenness (vegetative presence) is a novel and understudied protective factor for CVD and MetS, with emerging evidence suggesting that reductions in CVD and MetS could be achieved by optimizing environmental greenness. However, a complete understanding of “how” and “for whom” greenness provides cardiovascular health benefits has not been fully elucidated, with recent work now showing that environment and lifestyle exposure can interact with genetic susceptibility to CVD. However, no study to date has examined whether genetics moderates the relationship of environmental greenness exposure to CVD or MetS. The supplement therefore proposes to examine: (1) whether genetics moderates the relationship of greenness to cardiovascular health; (2) whether those participants with the greatest genetic risk for CVD show the greatest benefit of high greenness exposures when compared to those participants with lower genetic risk for CVD; and (3) which specific genetic variants may be contributing most to the moderating effects of genetics on cardiovascular health. Building on the parent study (R01-HL-148880), this proposed supplemental study will be the first to investigative whether a polygenic risk score (PRS) indicating a higher risk of CVD, moderates the effect of greenness on cardiovascular health. We will do so by simultaneously investigating the effects of the PRS and Greenness, and their interaction, on cardiovascular health using conditional logistic regression models as has been previously used to model the interaction of genetic risk scores and lifestyle factors on cardiovascular health in the Hispanic Community Health Study / Study of Latinos (HCHS/SOL) cohort. Therefore, the primary aim of the proposed supplement is to examine whether a polygenic risk score (PRS) indicating a higher risk of CVD, moderates the effect of greenness on cardiovascular health. We hypothesize that, when compared to participants in the lowest two tertiles of polygenic risk score (PRS) for cardiovascular outcomes, those participants in the highest tertile of PRS (i.e., showing the highest risk for CVD) will show a greater benefit of high greenness exposures on cardiovascular health, the latter measured via blood pressure, blood glucose, and lipid profile. Finally, a planned secondary analysis will seek to identify the specific genetic variants contributing to the moderating effects of PRS on the relationships of greenness to cardiovascular health. Identifying these genetic variants may help explain the mechanism underlying the greenness effect on cardiovascular health. Findings from this proposal will advance our understanding of how genetic risk for CVD may moderate the impact of greenness on cardiovascular health, which may be important for planning policy or environmental interventions (e.g., tree planting; parks) to best reduce the risk of CVD in Hispanics/Latinos.

Project Narrative (Public Health Relevance): Our prior research has influenced policy interventions (e.g., incorporated into redesign of zoning codes; greening interventions). Findings from the proposed supplemental grant may improve our understanding of whether genetics modifies the relationship of environmental greenness to Hispanics' cardiovascular health. Should findings reveal that individuals at high genetic risk for cardiovascular disease (CVD) benefit the most from higher greenness levels, then this may suggest policy interventions (e.g., tree planting) to reduce CVD in the most underserved populations, at risk for cardiovascular events due to both genetic risk and low greenery.