Background We sought to determine whether
mitochondrial DNA (
mtDNA) content can be used as markers for 12 key phenotypes among
cardiovascular disease patients, and whether these markers are valid across patients with diverse ancestries. Methods and Results
DNA was collected from the peripheral blood of 996
cardiovascular disease patients at the Cleveland Clinic. The
mtDNA copy number and
DNA-level variation were assessed from whole-genome sequence. Patients were also ascertained retrospectively for histories of 10 clinical events, as well as for maximum
stenosis and extent of disease at baseline. Self-reported race and maternal ancestry inferred from
mtDNA sequence were recorded.
MtDNA copy number and overall
mtDNA rare variant load were significantly lower in patients with histories of various adverse clinical events, and
mtDNA copy number was inversely correlated with extent of disease. Strong associations were also found between absence of rare variants in the genes MT-ATP6 and MT-COII and patient histories of
hyperlipidemia and
myocardial infarction, respectively. Importantly, associations were not ancestry dependent. Conclusions This study provides evidence that
mtDNA copy number in circulation is associated with a variety of
cardiovascular disease patient phenotypes. Results also suggest a protective role for some rare inherited
mtDNA variants. Overall, the study supports the potential of
mtDNA content and abundance as
biomarkers in
heart disease, in a manner that is valid across diverse ancestries.