Biological mechanisms underlying the relationships between environmental exposures and risk of respiratory and cardiovascular diseases

National Heart, Lung, And Blood Institute

Investigators

Linked publications & trials

Abstract

Accomplishments: 1) Submitted a manuscript on the association between urban-rural residential spectrum and risk of incident heart failure in the United Kingdom (UK) Biobank. We found that those living in less populated areas of England had significantly increased risk of heart failure compared to those in densely populated areas of Scotland. Additionally, we found that those with increased biological aging, as reflected by a biological health score, had increased risk of heart failure. The association between urban-rural spectrum and heart failure was partially mediated by increased biological aging. Our findings support better health care delivery to rural or less populated areas to mitigate the growing epidemic of heart failure the aging population of the UK. 2) Submitted a manuscript on the shared genetic etiology between heart failure and respiratory, inflammatory, autoimmune, and cardiovascular diseases in the UK Biobank. We found that heart failure shared common genetic susceptibility with several of these diseases, notably with asthma. We further investigated the role of biological aging reflected by leukocyte telomere length in these relationships as an effect modifier and mediator. We found negligible evidence that telomere length mediated the relationship between genetic susceptibility and heart failure risk. However, we found strong evidence that longer telomere length strengthened the relationship between asthma genetic susceptibility and heart failure, operating as an effect modifier. Our findings support the further investigation of genetics and telomere length in future risk stratification analyses. 3) Obtained approval and access to the Atherosclerosis Research in Communities study to conduct a study to characteristic loci-specific Alu retroelements, a biomarker of genomic instability, in whole exome sequencing data. We will link these predicted loci-specific Alu retroelements with future risk of cardiopulmonary outcomes and lung cancer.