Dataset Information

Mitochondrial DNA methylation and copy number predict body composition in a young female population.

ABSTRACT: BACKGROUND:Since both genomic and environmental factors are involved in obesity etiology, several studies about the influence of adiposity on both nuclear DNA and mitochondrial DNA methylation patterns have been carried out. Nevertheless, few evidences exploring the usage of buccal swab samples to study mitochondrial DNA epigenetics can be found in literature. METHODS:In this study, mitochondrial DNA from buccal swabs collected from a young Caucasian population (n?=?69) have been used to examine potential correlation between mitochondrial DNA copy number and methylation with body composition (BMI, WHtR and bioimpedance measurements). RESULTS:A negative correlation between mitochondrial DNA copy number and BMI was measured in females (p?=?0.028), but not in males. The mean percentage of D-loop methylation is significantly higher in overweight than in lean female subjects (p?=?0.003), and a specific CpG located in the D-loop shows per se an association with impaired body composition (p?=?0.004). Body composition impairment is predicted by a combined variable including mtDNA copy number and the D-loop methylation (AUC?=?0.785; p?=?0.009). CONCLUSIONS:This study corroborates the hypothesis that mitochondrial DNA carries relevant information about body composition. However, wider investigations able to validate the usage of mtDNA methylation from buccal swabs as a biomarker are warranted.

SUBMITTER: Bordoni L

PROVIDER: S-EPMC6883616 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Mitochondrial DNA methylation and copy number predict body composition in a young female population.

Bordoni Laura L Smerilli Vanessa V Nasuti Cinzia C Gabbianelli Rosita R

Journal of translational medicine 20191128 1

<h4>Background</h4>Since both genomic and environmental factors are involved in obesity etiology, several studies about the influence of adiposity on both nuclear DNA and mitochondrial DNA methylation patterns have been carried out. Nevertheless, few evidences exploring the usage of buccal swab samples to study mitochondrial DNA epigenetics can be found in literature.<h4>Methods</h4>In this study, mitochondrial DNA from buccal swabs collected from a young Caucasian population (n = 69) have been ...[more]

PMID: 31779622

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Project description: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 mechanism may be through regulation of nuclear gene expression via the modification of nuclear DNA (nDNA) methylation. METHODS:To investigate this hypothesis, we assessed the relationship between mtDNA-CN and nDNA methylation in 2507 African American (AA) and European American (EA) participants from the Atherosclerosis Risk in Communities (ARIC) study. To validate our findings, we assayed an additional 2528 participants from the Cardiovascular Health Study (CHS) (N?=?533) and Framingham Heart Study (FHS) (N?=?1995). We further assessed the effect of experimental modification of mtDNA-CN through knockout of TFAM, a regulator of mtDNA replication, via CRISPR-Cas9. RESULTS:Thirty-four independent CpGs were associated with mtDNA-CN at genome-wide significance (P?<?5?×?10-?8). Meta-analysis across all cohorts identified six mtDNA-CN-associated CpGs at genome-wide significance (P?<?5?×?10-?8). Additionally, over half of these CpGs were associated with phenotypes known to be associated with mtDNA-CN, including coronary heart disease, cardiovascular disease, and mortality. Experimental modification of mtDNA-CN demonstrated that modulation of mtDNA-CN results in changes in nDNA methylation and gene expression of specific CpGs and nearby transcripts. Strikingly, the "neuroactive ligand receptor interaction" KEGG pathway was found to be highly overrepresented in the ARIC cohort (P?=?5.24?×?10-?12), as well as the TFAM knockout methylation (P?= 4.41?×?10-?4) and expression (P?= 4.30?×?10-?4) studies. CONCLUSIONS:These results demonstrate that changes in mtDNA-CN influence nDNA methylation at specific loci and result in differential expression of specific genes that may impact human health and disease via altered cell signaling.

Project description:Copy number variation (CNV) is a major genetic polymorphism contributing to genetic diversity and human evolution. Clinical application of CNVs for diagnostic purposes largely depends on sufficient population CNV data for accurate interpretation. CNVs from general population in currently available databases help classify CNVs of uncertain clinical significance, and benign CNVs. Earlier studies of CNV distribution in several populations worldwide showed that a significant fraction of CNVs are population specific. In this study, we characterized and analyzed CNVs in 3,017 unrelated Thai individuals genotyped with the Illumina Human610, Illumina HumanOmniexpress, or Illumina HapMap550v3 platform. We employed hidden Markov model and circular binary segmentation methods to identify CNVs, extracted 23,458 CNVs consistently identified by both algorithms, and cataloged these high confident CNVs into our publicly available Thai CNV database. Analysis of CNVs in the Thai population identified a median of eight autosomal CNVs per individual. Most CNVs (96.73%) did not overlap with any known chromosomal imbalance syndromes documented in the DECIPHER database. When compared with CNVs in the 11 HapMap3 populations, CNVs found in the Thai population shared several characteristics with CNVs characterized in HapMap3. Common CNVs in Thais had similar frequencies to those in the HapMap3 populations, and all high frequency CNVs (>20%) found in Thai individuals could also be identified in HapMap3. The majorities of CNVs discovered in the Thai population, however, were of low frequency, or uniquely identified in Thais. When performing hierarchical clustering using CNV frequencies, the CNV data were clustered into Africans, Europeans, and Asians, in line with the clustering performed with single nucleotide polymorphism (SNP) data. As CNV data are specific to origin of population, our population-specific reference database will serve as a valuable addition to the existing resources for the investigation of clinical significance of CNVs in Thais and related ethnicities.

Dataset Information

Mitochondrial DNA methylation and copy number predict body composition in a young female population.

Publications

Mitochondrial DNA methylation and copy number predict body composition in a young female population.

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