D. Arking
6 Papers
D. Arking is an academic researcher. The author has contributed to research in topics: Mitochondrial DNA & Medicine. The author has an hindex of 1, co-authored 3 publications.
Chat about Author
Papers
The association between mitochondrial DNA copy number, low-density lipoprotein cholesterol, and cardiovascular disease risk
X L Liu,X. Sun,Y Zhang,Ming May Lai,Kerri L. Wiggins,L. Raffield,Lawrence F. Bielak,Wei Zhao,Achilleas N. Pitsillides,Jeffrey Haessler,Yu Zheng,Thomas W. Blackwell,J. Yao,Xu Guo,Yafang Qian,Bharat Thyagarajan,Nathan Pankratz,Steve Rich,Kent D. Taylor,Patricia A. Peyser,S. Heckbert,Sudha Seshadri,Eric Boerwinkle,M. Grove,Nicholas B. Larson,J. Smith,Vinitha Ramachandran,A. Fitzpatrick,Myriam Fornage,Jun Ding,April P. Carson,G. Abecasis,Josée Dupuis,Alexander P. Reiner,Charles Kooperberg,L. Hou,B. M. Psaty,J. S. Wilson,Daniel Levy,J. Rotter,J. C. Bis,Claudia L. Satizabal,D. Arking,C. Liu +43 more
TL;DR: High LDL underlies the complex relationships between vascular atherosclerosis and lower mtDNA CN, and finds no evidence supporting a causal association for lower mt DNA CN with higher CHD risk or higher LDL, but bi-directional univariable and multivariable MR analyses provided strong evidence indicating higher LDL level is causally associated with lower mitochondrial DNA copy number, and CHD was weakly associated with higher mtDNACN.
Air pollution exposure and mitochondrial DNA copy number in the UK Biobank
Yun Soo Hong,Stephanie L. Battle,Daniela Puiu,Wensong Shi,Nathan Pankratz,D. Zhao,D. Arking,Eliseo Guallar +7 more
TL;DR: The findings suggest that oxidative stress-induced mitochondrial dysfunction, reflected by reduced mtDNA-CN, may be an additional mechanism mediating the health effects of air pollution.
Association analysis of mitochondrial heteroplasmic variants and cardiometabolic traits
X. Sun,X. Liu,K. Bulekova,A. Pitsillides,X. Guo,Y. Qian,L. Raffield,J. Rotter,S. Rich,Gonçalo Abecasis,A. P. Carson,V. Ramachandran,J. C. Bis,B. M. Psaty,E. Boerwinkle,A. L. Fitzpatrick,C. L. Satizábal,D. Arking,D. Levy,TOPMed mtDNA working group +19 more
Abstract: Mitochondrial heteroplasmic variant has been increasingly recognized as a potential contributor to common complex diseases, yet its relationship with cardiometabolic disorders (CMDs) remains poorly understood. Leveraging deep whole-genome sequencing data from 16,882 participants across six multi-ancestry TOPMed cohorts, we systematically evaluated the associations between rare heteroplasmic variants and eight CMD traits, including body mass index (BMI), obesity, blood pressure, hypertension, blood glucose, diabetes, low-density lipoprotein (LDL), and hyperlipidemia. Using a previously developed statistical framework, we identified heteroplasmic variants according to three coding definitions and performed gene-based burden, SKAT, SKAT-O and ACAT-O tests within sixteen mitochondrial DNA (mtDNA) genes. We identified twelve significant gene-trait associations after Bonferroni correction, with consistent effect directions across coding definitions. The strongest association was observed between hyperlipidemia and heteroplasmic variants in CO1 gene (OR=0.28, 95% CI=(0.17, 0.46), p=3.4E-7) among EA (European Americans). Additional associations were detected for BMI, adjusted SBP (systolic blood pressure), BG (blood glucose), diabetes, and adjusted LDL. These findings highlight the contribution of heteroplasmic variation within mtDNA to cardiometabolic phenotypes and provide new insight into mitochondrial involvement in CMD pathophysiology.
Deleterious heteroplasmic mitochondrial mutations increase risk of overall and cancer-specific mortality
Stephanie L. Battle,Y. Hong,Wenwen Shi,Daniela Puiu,Vamsee Pillalamarri,Nathan Pankratz,Nicole J. Lake,Monkel Lek,Elena Guallar,D. Arking +9 more
TL;DR: The results indicate that mitochondria may have a functional role in certain cancers and mitochondrial heteroplasmic SNVs have the potential to serve as a prognostic markers for cancer incidence and outcome, especially for leukemia.
Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms
Yuan-Shu Hong,S. Pasca,D. Puiu,N. J. Lake,M. Lek,M. Ru,M. Grove,A. Prizment,C. E. Joshu,E. A. Platz,Elena Guallar,D. Arking,Lukasz P. Gondek +12 more
TL;DR: Heteroplasmy, in addition to being a marker of clonal expansion, may be a causal biomarker of MN development, with clinical utility in the general population.