Association of mitochondrial DNA copy number with cardiometabolic diseases in a large cross-sectional study of multiple ancestries

MedRxiv : the Preprint Server for Health Sciences
Chunyu LiuChunyu Liu

Abstract

The mitochondrial genome (mtDNA) is represented at variable copy number (CN) in human cells and plays essential roles in cellular metabolism. Previous studies reported inconsistent associations between mtDNA CN and cardiometabolic disease (CMD) traits. We determined the cross-sectional association of mtDNA CN measured in whole blood with several CMD traits in [~]66,100 individuals (mean age 60, 54% women, and 21% non-European ancestries). Cohort- and ancestry-specific association and meta-analysis were performed adjusting for trait-specific covariates and batch. Because white blood cell (WBC) count, a marker of subclinical inflammation, is associated with mtDNA CN level and multiple CMD traits, we further compared associations with and without adjustment for WBCs in a subset of individuals with WBCs. In meta-analysis without cell count adjustment in European ancestry (EA) participants (n=52,500), lower mtDNA CN was associated with higher odds of obesity (OR with 95% CI=1.13 (1.11, 1.16), P=3.3e-30) and hypertension (OR=1.05 (1.03, 1.08), P=4.0e-07). Further adjusting for WBCs in a subset of EA participants (N=44,100), associations became non-significant (P>0.05) for hypertension, attenuated for obesity (ORwithout cell counts=1....Continue Reading

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