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Identifying blood pressure loci whose effects are modulated by multiple lifestyle exposures.

ABSTRACT: Although multiple lifestyle exposures simultaneously impact blood pressure (BP) and cardiovascular health, most analysis so far has considered each single lifestyle exposure (e.g., smoking) at a time. Here, we exploit gene-multiple lifestyle exposure interactions to find novel BP loci. For each of 6,254 Framingham Heart Study participants, we computed lifestyle risk score (LRS) value by aggregating the risk of four lifestyle exposures (smoking, alcohol, education, and physical activity) on BP. Using the LRS, we performed genome-wide gene-environment interaction analysis in systolic and diastolic BP using the joint 2 degree of freedom (DF) and 1 DF interaction tests. We identified one genome-wide significant (p < 5 × 10^-8 ) and 11 suggestive (p < 1 × 10^-6 ) loci. Gene-environment analysis using single lifestyle exposures identified only one of the 12 loci. Nine of the 12 BP loci detected were novel. Loci detected by the LRS were located within or nearby genes with biologically plausible roles in the pathophysiology of hypertension, including KALRN, VIPR2, SNX1, and DAPK2. Our results suggest that simultaneous consideration of multiple lifestyle exposures in gene-environment interaction analysis can identify additional loci missed by single lifestyle approaches.

SUBMITTER: Osazuwa-Peters OL

PROVIDER: S-EPMC7717887 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Identifying blood pressure loci whose effects are modulated by multiple lifestyle exposures.

Osazuwa-Peters Oyomoare L OL Waken R J RJ Schwander Karen L KL Sung Yun Ju YJ de Vries Paul S PS Hartz Sarah M SM Chasman Daniel I DI Morrison Alanna C AC Bierut Laura J LJ Xiong Chengjie C de las Fuentes Lisa L Rao D C DC

Genetic epidemiology 20200329 6

Although multiple lifestyle exposures simultaneously impact blood pressure (BP) and cardiovascular health, most analysis so far has considered each single lifestyle exposure (e.g., smoking) at a time. Here, we exploit gene-multiple lifestyle exposure interactions to find novel BP loci. For each of 6,254 Framingham Heart Study participants, we computed lifestyle risk score (LRS) value by aggregating the risk of four lifestyle exposures (smoking, alcohol, education, and physical activity) on BP. U ...[more]

PMID: 32227373

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Project description:BackgroundThe risk for cardiovascular events increases within hours of near-roadway exposures. We aimed to determine the traffic-related air pollution (TRAP) and biological mechanisms involved and if reducing particulate matter <2.5 µm (PM2.5) inhalation is protective.MethodsFifty healthy-adults underwent multiple 2-hour near-roadway exposures (Tuesdays to Fridays) in Ann Arbor during 2 separate weeks (randomized to wear an N95 respirator during 1 week). Monday both weeks, participants rested 2 hours in an exam room (once wearing an N95 respirator). Brachial blood pressure, aortic hemodynamics, and heart rate variability were repeatedly measured during exposures. Endothelial function (reactive hyperemia index [RHI]) was measured post-exposures (Thursdays). Black carbon (BC), total particle count (PC), PM2.5, noise and temperature were measured throughout exposures.ResultsPM2.5 (9.3 ± 7.7 µg/m3), BC (1.3 ± 0.6 µg/m3), PC (8,375 ± 4,930 particles/cm3) and noise (69.2 ± 4.2 dB) were higher (P values <0.01) and aortic hemodynamic parameters trended worse while near-roadway (P values<0.15 vs. exam room). Other outcomes were unchanged. Aortic hemodynamics trended towards improvements with N95 respirator usage while near-roadway (P values<0.15 vs. no-use), whereas other outcomes remained unaffected. Higher near-roadway PC and BC exposures were associated with increases in aortic augmentation pressures (P values<0.05) and trends toward lower RHI (P values <0.2). N95 respirator usage did not mitigate these adverse responses (nonsignificant pollutant-respirator interactions). Near-roadway outdoor-temperature and noise were also associated with cardiovascular changes.ConclusionsExposure to real-world combustion-derived particulates in TRAP, even at relatively low concentrations, acutely worsened aortic hemodynamics. Our mixed findings regarding the health benefits of wearing N95 respirators support that further studies are needed to validate if they adequately protect against TRAP given their growing worldwide usage.

Project description:Smoking and alcohol consumption may compromise health by way of epigenetic modifications. Epigenetic signatures of alcohol and tobacco consumption could provide insights into the reversibility of phenotypic changes incurred with differing levels of lifestyle exposures. This study describes and validates two novel epigenetic signatures of tobacco (EpiTob) and alcohol (EpiAlc) consumption and investigates their association with disease outcomes. The epigenetic signatures, EpiTob and EpiAlc, were developed using data from the Swiss Kidney Project on Genes in Hypertension (SKIPOGH) (N = 689). Epigenetic and phenotypic data available from the 1921 (N = 550) and 1936 (N = 1091) Lothian Birth Cohort (LBC) studies, and two publicly available datasets on GEO Accession (GSE50660, N = 464; and GSE110043, N = 94) were used to validate the signatures. A multivariable logistic regression model, adjusting for age and sex, was used to assess the association between self-reported tobacco or alcohol consumption and the respective epigenetic signature, as well as to estimate the association between CVD and epigenetic signatures. A Cox proportional hazard model was used to estimate the risk of mortality in association with the EpiTob and EpiAlc signatures. The EpiTob signature was positively associated with self-reported tobacco consumption for current or never smokers with explained variance ranging from 0.49 (LBC1921) to 0.72 (LBC1936) (pseudo-R2). In the SKIPOGH, LBC1921 and LBC1936 cohorts, the epigenetic signature for alcohol consumption explained limited variance in association with self-reported alcohol status [i.e., non-drinker, moderate drinker, and heavy drinker] (pseudo-R2 = 0.05, 0.03 and 0.03, respectively), although this improved considerably when measuring self-reported alcohol consumption with standardized units consumed per week (SKIPOGH R2 = 0.21; LBC1921 R2 = 0.31; LBC1936 R2 = 0.41). Both signatures were associated with history of CVD in SKIPOGH and LBC1936, but not in LBC1921. The EpiTob signature was associated with increased risk of all-cause and lung-cancer specific mortality in the 1936 and 1921 LBC cohorts. This study found the EpiTob and EpiAlc signatures to be well-correlated with self-reported exposure status and associated with long-term health outcomes. Epigenetic signatures of lifestyle exposures may reduce measurement issues and biases and could aid in risk stratification for informing early-stage targeted interventions.

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Identifying blood pressure loci whose effects are modulated by multiple lifestyle exposures.

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Identifying blood pressure loci whose effects are modulated by multiple lifestyle exposures.

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