The proposed study examines susceptibility to the arrhythmogenic effects of particulate matter (PM) air pollution contributed by common genetic variation. Its rationale derives from the established, but heterogeneous association between ambient concentrations of PM air pollution and acute coronary heart disease (CHD) events, a widespread, but poorly understood threat to public health. Its focus is on resting, standard twelve-lead ECG measures that have been linked to ambient PM concentrations on the one hand, and to acute CHD events on the other. It will optimally leverage the genomic, environmental and electrocardiographic data from the Women's Health Initiative clinical trial (WHI CT), The SNP Health Association Resource project (SHARe, NHLBI-PB-2006-091), The Environmental Epidemiology of Arrhythmogenesis in WHI (5-R01-ES012238), the Atherosclerosis Risk in Communities (ARIC) study and the Population Architecture using Genomics and Epidemiology (PAGE) consortium. Specifically, it will examine measures of heart rate variability, ventricular repolarization, myocardial ischemia and ventricular ectopy within seven distinct subpopulations evaluated between 1987 and 2004. The seven subpopulations include: (1) 5148 black women, (2) 2002 Hispanic women, and (3) 1507 white women with and 1507 without ventricular ectopy in the WHI CT;and in the ARIC study, (4) 2615 black women, (5) 5989 white women, (6) 1621 black men, and (7) 5369 white men. Subpopulations 1-7 will be used to independently identify gene-by-environment interactions between approximately 106 single nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array and daily mean ambient PM concentrations spatially interpolated at geocoded participant addresses. SNP main effects will also be investigated. The intramurally co-funded analyses will be well-powered and appropriately adjusted for multiple comparisons. Anticipated findings will provide a foundation for examining the consistency of associations across race and gender. Collectively, they will advance understanding of genetic susceptibility to and the pathophysiological mechanisms underlying PM-mediated arrhythmogenesis in an ethnically and geographically representative population of 25,758 uniformly well-characterized participants living in U.S. Environmental Protection Agency (EPA) Regions 1-10. The advance will provide insight into the proportion of PM-attributable ECG abnormalities that could be reduced by establishing and complying with stricter National Ambient Air Quality Standards.
The proposed study will efficiently advance understanding of genetic susceptibility to and the pathophysiological mechanisms underlying PM-mediated arrhythmogenesis in an ethnically and geographically representative population of 25,758 uniformly well-characterized participants living in U.S. Environmental Protection Agency (EPA) Regions 1-10. Its rationale derives from the established, but heterogeneous association between ambient levels of particulate matter air pollution and acute coronary heart disease events, a widespread, but poorly understood threat to public health.
|Seyerle, A A; Sitlani, C M; Noordam, R et al. (2017) Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology. Pharmacogenomics J :|
|Kerr, Kathleen F; Avery, Christy L; Lin, Henry J et al. (2017) Genome-wide association study of heart rate and its variability in Hispanic/Latino cohorts. Heart Rhythm 14:1675-1684|
|Gondalia, Rahul; Avery, Christy L; Napier, Melanie D et al. (2017) Genome-wide Association Study of Susceptibility to Particulate Matter-Associated QT Prolongation. Environ Health Perspect 125:067002|
|Noordam, Raymond; Sitlani, Colleen M; Avery, Christy L et al. (2017) A genome-wide interaction analysis of tricyclic/tetracyclic antidepressants and RR and QT intervals: a pharmacogenomics study from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. J Med Genet 54:313-323|
|Evans, Daniel S; Avery, Christy L; Nalls, Mike A et al. (2016) Fine-mapping, novel loci identification, and SNP association transferability in a genome-wide association study of QRS duration in African Americans. Hum Mol Genet 25:4350-4368|
|Deo, R; Nalls, M A; Avery, C L et al. (2013) Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: a genome-wide association study of 13,372 participants. Heart Rhythm 10:401-8|
|Smith, J Gustav; Avery, Christy L; Evans, Daniel S et al. (2012) Impact of ancestry and common genetic variants on QT interval in African Americans. Circ Cardiovasc Genet 5:647-55|
|Butler, Anne M; Yin, Xiaoyan; Evans, Daniel S et al. (2012) Novel loci associated with PR interval in a genome-wide association study of 10 African American cohorts. Circ Cardiovasc Genet 5:639-46|