Abstract P261: Genome-wide Association Study of Susceptibility to Particulate Matter-associated Reduced Heart Rate Variability
Background: Heart rate variability (HRV) is a heritable electrocardiographic measure of cardiac autonnomic control that is consistently and inversely associated with ambient particulate matter (PM) air pollution and risk of both incident cardiovascular disease, and death. However, genetic susceptibility to PM-associated decreases in HRV has not been characterized.
Methods: To characterize such susceptibility in a genome-wide context, we conducted cohort-, race/ethnicity-, and sex-stratified longitudinal analyses of ten Women’s Health Initiative clinical trials and Atherosclerosis Risk in Communities Study subpopulations (total n: 27,121; mean age: 64.6 yr; 81% female; 25% black; 7% Hispanic; mean visits/person: 2.5). In each subpopulation, we log-transformed three previously validated and reliable measures of HRV: RR interval duration (RR); root mean square of successive differences in normal-to-normal RR (RMSSD); and standard deviation of normal-to-normal RR (SDNN). We also estimated mean concentrations of PM < 10 μm on the day of and before HRV measurement. We then used generalized estimating equations (GEE) methods adapted for low prevalence exposure to leverage the repeated measures of HRV and PM10. The GEE models estimated interactions between approximately 2.5 million single nucleotide polymorphisms (SNPs) and PM10 concentrations dichotomized at subpopulation-specific 90th percentiles, while adjusting for age, geographic region or center, season, calendar year, and ancestry. We combined the SNP x PM10 interaction estimates in a Bayesian meta-analysis accounting for ancestral heterogeneity to identify trans-ethnic interactions exceeding genome-wide thresholds: log10 Bayes Factor (BF) > 6 and posterior probability of heterogeneity (PHet) < 0.5.
Results: Preliminary analyses of RMSSD provided suggestive evidence of a trans-ethnically important interaction at five SNPs on one locus. The lead SNP (rs17809071; T allele frequency range: 3-16%) is located on chromosome 4, 120 kilobases downstream from SPRY1 (log10BF = 5.31; PHet = 0.14). SPRY1 encodes sprouty receptor tyrosine kinase signaling antagonist 1 which is expressed in cardiac fibroblasts, antagonizes cytokine-induced epicardial fibrosis, and inhibits adipogenesis.
Conclusions: Findings from this genome-wide association study of SNP x PM10 interactions suggest that genetic factors may affect susceptibility to PM10-associated decreases in HRV among racially/ethnically diverse populations of men and women protected by the U.S. Environmental Protection Agency under the Clean Air Act.
Author Disclosures: R. Gondalia: None. C.L. Avery: None. M.D. Napier: None. R. Giráldez: None. J.D. Stewart: None. C.M. Sitlani: None. Y. Li: None. J. Roach: None. K.E. North: None. A.P. Reiner: None. Z. Zhang: None. L. Tinker: None. D. Liao: None. E.A. Whitsel: None. M. Investigators: None.
- © 2016 by American Heart Association, Inc.