Association of mitochondrial DNA copy number with cardiometabolic diseases in a large cross-sectional study of multiple ancestries
Ryan J Longchamps,
Achilleas N Pitsillides,
Steve S Rich,
Kent D. Taylor,
Patricia A. Peyser,
Susan R. Heckbert,
Megan L Grove,
Jennifer A. Smith,
Ramachandran S Vasan,
Annette L. Fitzpatrick,
Bruce M Psaty,
James G Wilson,
Jerome I. Rotter,
Joshua C. Bis,
Claudia L. Satizabal,
Dan E Arking,
Posted 24 Apr 2020
medRxiv DOI: 10.1101/2020.04.20.20016337
Posted 24 Apr 2020
Aims We tested the hypothesis that mitochondrial DNA copy number (CN) is associated with cardiometabolic disease (CMD) traits. Methods and results We determined the cross-sectional association of mtDNA CN measured in whole blood with several CMD traits in 65,996 individuals (mean age 60, 54% women, and 79% European descent). Cohort- and ancestry/ethnicity-specific association analysis was performed adjusting for trait- and cohort-specific covariates. Age was slightly positively associated with age (0.03 s.d. / 10 years (95% CI=0.01, 0.05)) before 65 years, while every 10 years older age was associated with 0.14 s.d. lower level of mtDNA CN after 65 years (95% CI= -0.18, -0.10). In meta-analysis without adjustment for white blood cell (WBC) and differential count in participants of European descent (N=52,491), low mtDNA CN was associated with increased 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 WBC and differential count in the same participants of European descent (N=44,035), associations became non-significant (P>0.05) for hypertension, attenuated for obesity (ORwithout cell count=1.15 (1.12, 1.18) versus ORcell count=1.06 (1.03, 1.08)) but strengthened for hyperlipidemia (ORwithout cell counts =1.03 (1.00, 1.06) versus ORcell counts =1.06 (1.03, 1.09)). The magnitude and directionality of most associations were consistent between participants of European descent and other ethnicity/ancestry origins. Conclusion Low levels of mtDNA CN in peripheral blood were associated with an increased risk of CMD diseases. Key words: mitochondrial DNA copy number, cardiometabolic disease, whole genome sequencing
- Downloaded 277 times
- Download rankings, all-time:
- Site-wide: 85,582
- In epidemiology: 3,506
- Year to date:
- Site-wide: 28,145
- Since beginning of last month:
- Site-wide: 19,923
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!