Dataset Information

Peripheral Mitochondrial DNA Copy Number is Increased in Korean Attention-Deficit Hyperactivity Disorder Patients.

ABSTRACT: The involvement of mitochondrial dysfunction in the pathophysiology of attention-deficit hyperactivity disorder (ADHD) has been suggested in several reports. Mitochondrial DNA (mtDNA) copy number as well as methylation of the D-loop region and peroxisome-proliferator-activated receptor ? co-activator-1? (PPARGC1A) are considered biomarkers for mitochondrial dysfunction. We compared the mtDNA copy number and methylation ratio of the D-loop region and PPARGC1A between ADHD patients and controls and also among ADHD subtypes. The present study included 70 subjects with ADHD and 70 age- and gender-matched healthy controls (HCs). We measured the relative mtDNA copy number in peripheral blood cells using quantitative polymerase chain reaction (qPCR), and the methylation ratio was measured using methylation-specific PCR (MSP) after bisulfite conversion. The relative mtDNA copy number was significantly higher in ADHD patients than in HCs (p = 0.028). The mtDNA methylation ratio of PPARGC1A was decreased in ADHD patients compared with HCs (p = 0.008). After adjusting for IQ level, only the mtDNA copy number differed between the ADHD and HCs (p = 0.01). There was a significant difference in the methylation ratio of PPARGC1A among ADHD subtypes. These results suggest the possible involvement of mitochondrial dysfunction in the pathophysiology of ADHD. Further large cohort studies investigating the correlation between clinical markers and biomarkers of mitochondrial dysfunction are warranted.

SUBMITTER: Kim JI

PROVIDER: S-EPMC6656858 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Peripheral Mitochondrial DNA Copy Number is Increased in Korean Attention-Deficit Hyperactivity Disorder Patients.

Kim Johanna Inhyang JI Lee Soo-Young SY Park Mira M Kim Si Yeon SY Kim Jae-Won JW Kim Soon Ae SA Kim Bung-Nyun BN

Frontiers in psychiatry 20190718

The involvement of mitochondrial dysfunction in the pathophysiology of attention-deficit hyperactivity disorder (ADHD) has been suggested in several reports. Mitochondrial DNA (mtDNA) copy number as well as methylation of the D-loop region and peroxisome-proliferator-activated receptor γ co-activator-1α (<i>PPARGC1A</i>) are considered biomarkers for mitochondrial dysfunction. We compared the mtDNA copy number and methylation ratio of the D-loop region and <i>PPARGC1A</i> between ADHD patients a ...[more]

PMID: 31379624

Similar Datasets

Project description:While childhood attention-deficit/hyperactivity disorder (ADHD) is more prevalent in males than females, genetic contributors to this effect have not been established. Here, we explore sex differences in the contribution of common and/or rare genetic variants to ADHD. Participants were from the Adolescent Brain and Cognitive Development study (N = 1253 youth meeting DSM-5 criteria for ADHD [mean age = 11.46 years [SD = 0.87]; 31% female] and 5577 unaffected individuals [mean age = 11.42 years [SD = 0.89]; 50% female], overall 66% White, non-Hispanic (WNH), 19% Black/African American, and 15% other races. Logistic regression tested for interactions between sex (defined genotypically) and both rare copy number variants (CNV) and polygenic (common variant) risk in association with ADHD. There was a significant interaction between sex and the presence of a CNV deletion larger than 200 kb, both in the entire cohort (β = -0.74, CI = [-1.27 to -0.20], FDR-corrected p = 0.048) and, at nominal significance levels in the WNH ancestry subcohort (β = -0.86, CI = [-1.51 to -0.20], p = 0.010). Additionally, the number of deleted genes interacted with sex in association with ADHD (whole cohort. β = -0.13, CI = [-0.23 to -0.029], FDR-corrected p = 0.048; WNH. β = -0.17, CI = [-0.29 to -0.050], FDR-corrected p = 0.044) as did the total length of CNV deletions (whole cohort. β = -0.12, CI = [-0.19 to -0.044], FDR-corrected p = 0.028; WNH. β = -0.17, CI = [-0.28 to -0.061], FDR-corrected p = 0.034). This sex effect was driven by increased odds of childhood ADHD for females but not males in the presence of CNV deletions. No similar sex effect was found for CNV duplications or polygenic risk scores. The association between CNV deletions and ADHD was partially mediated by measures of cognitive flexibility. In summary, CNV deletions were associated with increased odds for childhood ADHD in females, but not males.

Dataset Information

Peripheral Mitochondrial DNA Copy Number is Increased in Korean Attention-Deficit Hyperactivity Disorder Patients.

Publications

Peripheral Mitochondrial DNA Copy Number is Increased in Korean Attention-Deficit Hyperactivity Disorder Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets