In the Wrong Place with the Wrong SNP

Abstract

Background Sudden cardiac arrest has been linked independently both to stressful neighborhood conditions and to polymorphisms in the ADRB2 gene. The ADRB2 gene mediates sympathetic activation in response to stress. Therefore, if neighborhood conditions cause cardiac arrest through the stress pathway, the ADRB2 variant may modify the association between neighborhood conditions such as socioeconomic deprivation and incidence of cardiac arrest. Methods The Cardiac Arrest Blood Study Repository is a population-based repository of specimens and other data from adult cardiac arrest patients residing in King County, Washington. Cases (n = 1,539) were 25- to 100-year-old individuals of European descent who experienced out-of-hospital cardiac arrest from 1988 to 2004. Interactions between neighborhood conditions and the ADRB2 genotype on cardiac arrest risk were assessed in a case-only study design. Gene–environment independence was assessed in blood samples obtained from King County residents initially contacted by random-digit dialing. Results Fewer than 4% of study subjects resided in socioeconomically deprived neighborhoods. Nonetheless, the case-only analysis indicated the presence of supra-multiplicative interaction of socioeconomic deprivation and the homozygous Gln27Glu variant [Case-only odds ratio (OR): 1.8 (95% confidence interval [CI]: 1.0, 2.9)]. Interactions between population density and the homozygous Gln27Glu variant were weaker [Case-only OR: 1.2, (95% CI: 0.97, 1.5)]. Conclusions Findings support a supra-multiplicative interaction between the Gln27Glu ADRB2 variant and socioeconomic deprivation among individuals of European descent. This result is consistent with the hypothesis that the elevation in cardiac arrest risk associated with socioeconomic deprivation operates through the stress pathway.

Neighborhood food environment, dietary fatty acid biomarkers, and cardiac arrest risk

“…In conclusion, living in a denser retail environment was associated with higher cardiac arrest risk but lower trans fatty acids concentrations in RBC membranes, providing only partial support for the hypothesis that residing closer to unhealthy food outlets explains the link between dense environment and cardiac arrest. While our findings are preliminary, they suggest that other spatial correlates of dense retail environments not directly linked to food consumption, such as air pollution exposure (Link and Dockery, 2010) or stressful neighborhood conditions,(Mooney et al, 2016) may pose more promising directions for future research.…”

Medical facilities in the neighborhood and incidence of sudden cardiac arrest

“…Similarly, because associations between home census tract and response time independent of SCA location are unexpected unless there was unmeasured confounding by neighborhood selection, we repeated our analysis of survival after SCA using a subsample of participants whose VF-SCA events occurred outside of their home census tract (n=572, 36% of VF-SCA cases). Because of prior indications that SCA risk may be modified by neighborhood SES [23], we explored effect modification by neighborhood SES for the primary analyses by including an interaction term for cardiac-promoting medical facilities exposure and SES.…”

Nature-Based Solutions for Cities

“…Examining these differential patterns may strengthen the evidence for specific causal pathways. For example, place-based stressors may have a greater effect on health outcomes among individuals with stress-pathway genetic susceptibility (Dick, 2011;Mooney et al, 2016). While prior work has considered area-based socioeconomic conditions, a parallel finding for a stress pathway gene-environment interaction with NBS would support the importance of NBS in removing or allowing recovery from stressors.…”