A5063756055- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Genetic Associations and Epidemiology
- Metabolomics and Mass Spectrometry Studies
- Epigenetics and DNA Methylation
- Cardiovascular Function and Risk Factors
- Diet and metabolism studies
- RNA modifications and cancer
- Genetic Mapping and Diversity in Plants and Animals
- Eating Disorders and Behaviors
- Genomics and Rare Diseases
- Cardiovascular Health and Risk Factors
- Genomic variations and chromosomal abnormalities
- Nutrition, Genetics, and Disease
- Child Nutrition and Feeding Issues
- Sleep and related disorders
- Cardiac electrophysiology and arrhythmias
- CRISPR and Genetic Engineering
- Health, Environment, Cognitive Aging
- Genetic Syndromes and Imprinting
- Gene expression and cancer classification
- Atrial Fibrillation Management and Outcomes
- Cardiac Imaging and Diagnostics
- HIV-related health complications and treatments
- Liver Disease Diagnosis and Treatment
Massachusetts General Hospital
2021-2024
Broad Institute
2021-2023
Harvard University
2023
Johns Hopkins Medicine
2017-2021
Johns Hopkins University
2017-2021
McGill University
2020
Château de Longchamp
2018
National Institutes of Health
2014
National Institute of Nursing Research
2014
Mitochondrial dysfunction is a core component of the aging process and may play key role in atherosclerotic cardiovascular disease. DNA copy number (mtDNA-CN), which represents mitochondria per cell mitochondrial genomes mitochondrion, an indirect biomarker function.To determine whether mtDNA-CN, measured easily accessible tissue (buffy coat/circulating leukocytes), can improve risk classification for disease (CVD) help guide initiation statin therapy primary prevention CVD.Prospective,...
Mitochondrial DNA copy number (mtDNA-CN), a measure of the mitochondrial genomes per cell, is minimally invasive proxy for function and has been associated with several aging-related diseases. Although quantitative real-time PCR (qPCR) current gold standard method measuring mtDNA-CN, mtDNA-CN can also be measured from genotyping microarray probe intensities sequencing read counts. To conduct comprehensive examination on performance these methods, we use known correlates (age, sex, white...
Mitochondrial DNA copy number (mtDNA-CN) has been associated with a variety of aging-related diseases, including all-cause mortality. However, the mechanism by which mtDNA-CN influences disease is not currently understood. One such may be through regulation nuclear gene expression via modification (nDNA) methylation.
Mitochondrial DNA copy number (mtDNA-CN) is a proxy for mitochondrial function and associated with aging-related diseases. However, it unclear how mtDNA-CN measured in blood can reflect diseases that primarily manifest other tissues. Using the Genotype-Tissue Expression Project, we interrogated relationships between whole gene expression from 47 additional tissues 419 individuals. was significantly of 700 genes blood, including nuclear required mtDNA replication. Significant enrichment...
Genome-wide association studies (GWASs) have identified tens of thousands genetic loci associated with human complex traits. However, the majority GWASs were conducted in individuals European ancestries. Failure to capture global diversity has limited genomic discovery and impeded equitable delivery knowledge diverse populations. Here we report findings from 102,900 across 36 quantitative traits Taiwan Biobank (TWB), a major biobank effort that broadens population East Asia. We 968 novel...
Abstract Genome-wide association studies (GWAS) of human complex traits or diseases often implicate genetic loci that span hundreds thousands variants, many which have similar statistical significance. While fine-mapping in individuals European ancestries has made important discoveries, cross-population the potential to improve power and resolution by capitalizing on genomic diversity across ancestries. Here we present SuSiEx, an accurate computationally efficient method for fine-mapping,...
Sudden cardiac death (SCD) is a major public health burden. Mitochondrial dysfunction has been implicated in wide range of cardiovascular diseases including cardiomyopathy, heart failure, and arrhythmias, but it unknown if also contributes to SCD risk. We sought examine the prospective association between mtDNA copy number (mtDNA-CN), surrogate marker mitochondrial function, risk.We measured baseline mtDNA-CN 11 093 participants from Atherosclerosis Risk Communities (ARIC) study. was...
Mitochondrial DNA (mtDNA) is present in multiple copies human cells. We evaluated cross-sectional associations of whole blood mtDNA copy number (CN) with several cardiometabolic disease traits 408,361 participants ancestries TOPMed and UK Biobank. Age showed a threshold association CN: among younger (<65 years age), each additional 10 age was associated 0.03 standard deviation (s.d.) higher level CN (P = 0.0014) versus 0.14 s.d. lower 1.82 × 10-13) older (≥65 years). At levels, we found...
Abstract Background Mechanistic studies suggest that mitochondria DNA (mtDNA) dysfunction may be associated with increased risk of atrial fibrillation (AF). The association between mtDNA copy number (mtDNA-CN) and incident AF in the general population, however, remains unknown. Methods We conducted prospective analyses 19,709 participants from Atherosclerosis Risk Communities Study (ARIC), Multi-Ethnic (MESA), Cardiovascular Health (CHS). mtDNA-CN peripheral blood was calculated probe...
Low mitochondrial DNA (mtDNA) copy number (CN) is a predictor of adverse aging outcomes, and its status may be altered in human immunodeficiency virus (HIV)-infected persons. This study evaluated the cross-sectional longitudinal change mtDNA CN by HIV markers.mtDNA was measured ALIVE (AIDS Linked to Intravenous Experience) cohort persons with history injecting drugs. Multivariable linear regression models controlling for demographic characteristics, behavior, hepatitis C (HCV) seropositivity...
Introduction Mitochondrial DNA copy number (mtDNA-CN) is a measure of mitochondrial dysfunction and associated with diabetes in experimental models. To explore the temporality diabetes, we estimated prevalent incident association mtDNA-CN diabetes. Research design methods We assessed associations measured from buffy coat stratified by race, 8954 white 2444 black participants Atherosclerosis Risk Communities (ARIC) study, an observational cohort study. Follow-up for analyses was complete...
Abstract Genome-wide association studies (GWAS) have identified tens of thousands genetic loci associated with human complex traits and diseases 1,2 . However, the majority GWAS were conducted in individuals European ancestry 3 Failure to capture global diversity has limited biological discovery impeded equitable delivery genomic knowledge diverse populations 4 Here we report findings from 102,900 across 36 quantitative Taiwan Biobank (TWB), a major biobank effort that broadens population...
Sleep quality and genetics may contribute to the etiology of gastrointestinal (GI) symptoms. Individuals with impaired sleep often have a number associated symptoms including chronic abdominal pain (CAP). The current study examined interactions brain-derived neurotrophic factor (BDNF) genotype in persons CAP healthy controls. In addition, associations among quality, BDNF genotype, gene expression were explored participants.
Abstract Aims We tested the hypothesis that mitochondrial DNA copy number (CN) is associated with cardiometabolic disease (CMD) traits. Methods and results determined cross-sectional association of mtDNA CN measured in whole blood several CMD traits 65,996 individuals (mean age 60, 54% women, 79% European descent). Cohort- ancestry/ethnicity-specific analysis was performed adjusting for trait- cohort-specific covariates. Age slightly positively (0.03 s.d. / 10 years (95% CI=0.01, 0.05))...
ABSTRACT Background Mitochondrial DNA copy number (mtDNA-CN) can be used as a proxy for mitochondrial function and is associated with of aging-related diseases. However, it unclear how mtDNA-CN measured in blood reflect risk diseases that primarily manifest other tissues. Using the Genotype-Tissue Expression Project, we interrogated relationships between whole gene expression from well 47 additional Results We evaluated associations blood-derived 418 individuals, correcting known confounders...
Background: Atrial fibrillation (AF) is the most common clinical arrhythmia. Molecular studies suggest that mitochondrial dysfunction associated with increased risk of AF through reduced production adenosine triphosphate and reactive oxidative species. Mitochondrial DNA copy number (mtDNA CN), a marker function, has been found to be sudden cardiac death cardiovascular disease (CVD) in ARIC. However, association between mtDNA CN incident general population unknown. Objective: To examine...
ABSTRACT Background Mitochondrial DNA copy number (mtDNA-CN) has been associated with a variety of aging-related diseases, including all-cause mortality. However, the mechanism by which mtDNA-CN influences disease is not currently understood. One such may be through regulation nuclear gene expression via modification (nDNA) methylation. Methods To investigate this hypothesis, we assessed relationship between and nDNA methylation in 2,507 African American (AA) European (EA) participants from...
Abstract Background Mechanistic studies suggests that mitochondria DNA (mtDNA) dysfunction may be associated with increased risk of atrial fibrillation (AF). The association between mtDNA copy number (mtDNA-CN) and incident AF in the general population, however, remains unknown. Methods We conducted prospective analyses 19,709 participants from Atherosclerosis Risk Communities Study (ARIC), Multi-Ethnic (MESA) Cardiovascular Health (CHS). mtDNA-CN peripheral blood was calculated probe...