title: In the Wrong Place with the Wrong SNP: The Association Between Stressful Neighborhoods and Cardiac Arrest Within Beta-2-adrenergic Receptor Variants.
abstract: 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.
  
  
  
  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.
  
  
  
  Fewer than 4% of study subjects resided in socioeconomically deprived neighborhoods. Nonetheless, the case-only analysis indicated the presence of supramultiplicative interaction of socioeconomic deprivation and the homozygous Gln27Glu variant (case-only odds ratio: 1.8 [95% confidence interval: 1.0, 2.9]). Interactions between population density and the homozygous Gln27Glu variant were weaker (case-only odds ratio: 1.2 [95% confidence interval: 0.97, 1.5]).
  
  
  
  Findings support a supramultiplicative 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.
authors.affiliation: From the aDepartment of Epidemiology, Columbia University, New York, NY; bCardiovascular Health Research Unit, University of Washington, Seattle, WA; cSeattle Children's Research Institute, Seattle, WA; dIDEAS Center, VA Salt Lake City Health Care System, Salt Lake City, UT; eNew York Academy of Medicine, New York, NY; fDepartment of Biostatistics, University of Washington, Seattle, WA; gCardiovascular Research Institute, University of California, San Francisco, CA; and hGarvan Institute of Medical Research, Sydney, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Mooney
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Grady
authors.forename: Nona
authors.initials: N
authors.lastname: Sotoodehnia
authors.forename: Rozenn N
authors.initials: RN
authors.lastname: Lemaitre
authors.forename: Erin R
authors.initials: ER
authors.lastname: Wallace
authors.forename: April F
authors.initials: AF
authors.lastname: Mohanty
authors.forename: Jean
authors.initials: J
authors.lastname: Yee
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Rea
authors.forename: Barbara
authors.initials: B
authors.lastname: McKnight
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.forename: Angel C Y
authors.initials: AC
authors.lastname: Mak
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hesselson
authors.forename: Gina S
authors.initials: GS
authors.lastname: Lovasi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D058687:Out-of-Hospital Cardiac Arrest / Q000453:epidemiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012111:Residence Characteristics / Q000706:statistics & numerical data*; D012959:Socioeconomic Factors; D014861:Washington / Q000453:epidemiology; D044465:White People / Q000235:genetics*
chemical_list: C553443:ADRB2 protein, human; D018343:Receptors, Adrenergic, beta-2