Abstract P451: Aircraft Noise Exposure As A Novel Risk Factor For Clonal Hematopoiesis Of Indeterminate Potential

Abstract

Background: Although the etiology of clonal hematopoiesis of indeterminate potential (CHIP) remains unclear, CHIP-defining somatic mutations within hematopoietic stem cells appear to expand peripheral blood leukocyte populations, promote inflammation, and thereby increase cardiovascular disease (CVD) risk. Moreover, high noise exposures have been linked to chromosomal aberrations in bone marrow and DNA repair in peripheral blood leukocytes. We therefore examined the potential of aircraft noise exposure as a novel risk factor for CHIP. Methods: We leveraged cross-sectional data on 10,050 postmenopausal women without prior hematologic malignancy in a Women’s Health Initiative (WHI) ancillary study of 5,309 women with stroke and/or venous thromboembolic disease and 4,741 controls. We ascertained CHIP using Trans-Omics for Precision Medicine (TOPMed) whole-genome sequencing data, the GATK Mu TECT2 somatic variant caller, a pre-specified list of leukemogenic driver mutations in 74 genes, and a threshold variant allele frequency of > 0.02. In cooperation with the Federal Aviation Administration, we generated day-night-level (DNL) noise contours around 90 major U.S. airports using the Aviation Environmental Design Tool noise modelling software. The DNL imposes a penalty for nighttime noise exposure and is the primary means for assessing and regulating noise exposure in the U.S. We estimated geocoded participant address-specific, annual average DNL aircraft noise exposures in decibels (dB) from the contours on the day of blood draw and categorized individuals as exposed or non-exposed (DNL ≥ or < 45dB). We estimated the noise-related risk of CHIP as an odds ratio, 95% confidence interval (OR, 95% CI) using logistic regression before and after adjustment for age, race / ethnicity, case-control status, smoking, alcohol use, body mass index, physical activity, hearing loss, education, and neighborhood socioeconomic status. Results: Among this population of postmenopausal women (Mean age: 68.7 years; White: 82.1%; African American: 12.3%), 19.4% were exposed to aircraft noise, and 8.4% had CHIP. The age-adjusted CHIP proportion was higher among whites (8.1%) than African Americans (7.3%) and other racial/ethnic groups (6.4%). CHIP was also more common among women aged ≥ 70 years (11.5%) than those aged 60-69 years (7.5%) or 50-59 years (3.8%). Compared to non-exposed women, those exposed to aircraft noise were not at increased risk of CHIP: OR unadjusted (95% CI) = 0.95 (0.80, 1.14) and OR adjusted (95% CI) = 0.97 (0.81, 1.16). Results were insensitive to dichotomization of noise exposure at 55 dB and further exclusion of women with hearing loss. Conclusion: Our study found no evidence of an association between aircraft noise and CHIP suggesting that aircraft noise may not be a factor contributing to CHIP-defining somatic mutations linked to CVD.