Dataset Information

Mitochondrial DNA haplogroups and risk of attention deficit and hyperactivity disorder in European Americans.

ABSTRACT: Although mitochondrial dysfunction has been implicated in the pathophysiology of attention deficit and hyperactivity disorder ADHD, the role of mitochondrial DNA (mtDNA) has not been extensively investigated. To determine whether mtDNA haplogroups influence risk of ADHD, we performed a case-control study comprising 2076 ADHD cases and 5078 healthy controls, all of whom were European decedents recruited from The Children's Hospital of Philadelphia (CHOP). Associations between eight major European mtDNA Haplogroups and ADHD risk were assessed in three independent European cohorts. Meta-analysis of the three studies indicated that mtDNA haplogroups K (odds ratio?=?0.69, P?=?2.24?×?10-4, Pcorrected?=?1.79?×?10-3) and U (odds ratio?=?0.77, P?=?8.88?×?10-4, Pcorrected?=?7.11?×?10-3) were significantly associated with reduced risk of ADHD. In contrast, haplogroup HHV* (odds ratio?=?1.18, P?=?2.32?×?10-3, Pcorrected?=?0.019) was significantly associated with increased risk of ADHD. Our results provide novel insight into the genetic basis of ADHD, implicating mitochondrial mechanisms in the pathophysiology of this relatively common psychiatric disorder.

SUBMITTER: Chang X

PROVIDER: S-EPMC7608630 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Mitochondrial DNA haplogroups and risk of attention deficit and hyperactivity disorder in European Americans.

Chang Xiao X Liu Yichuan Y Mentch Frank F Glessner Joseph J Qu Huiqi H Nguyen Kenny K Sleiman Patrick M A PMA Hakonarson Hakon H

Translational psychiatry 20201102 1

Although mitochondrial dysfunction has been implicated in the pathophysiology of attention deficit and hyperactivity disorder ADHD, the role of mitochondrial DNA (mtDNA) has not been extensively investigated. To determine whether mtDNA haplogroups influence risk of ADHD, we performed a case-control study comprising 2076 ADHD cases and 5078 healthy controls, all of whom were European decedents recruited from The Children's Hospital of Philadelphia (CHOP). Associations between eight major European ...[more]

PMID: 33139694

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Project description:Individuals with attention deficit hyperactivity disorder (ADHD) show gray matter volume (GMV) reduction in the putamen. KTN1 variants may regulate kinectin 1 expression in the putamen and influence putamen structure and function. We aim to test the hypothesis that the KTN1 variants may represent a genetic risk factor of ADHD. Two independent family-based Caucasian samples were analyzed, including 922 parent-child trios (a total of 2,757 subjects with 924 ADHD children) and 735 parent-child trios (a total of 1,383 subjects with 613 ADHD children). The association between ADHD and a total of 143 KTN1 SNPs was analyzed in the first sample, and the nominally-significant (p < .05) risk SNPs were classified into independent haplotype blocks. All SNPs, including imputed SNPs within these blocks, and haplotypes across each block, were explored for replication of associations in both samples. The potential biological functions of all risk SNPs were predicted using a series of bioinformatics analyses, their regulatory effects on the putamen volumes were tested, and the KTN1 mRNA expression was examined in three independent human putamen tissue samples. We found that fifteen SNPs were nominally associated with ADHD (p < .05) in the first sample, and three of them remained significant even after correction for multiple testing (1.3 × 10-10 ≤ p ≤ 1.2 × 10-4 ; α = 2.5 × 10-3 ). These 15 risk SNPs were located in five haplotype blocks, and 13 SNPs within four of these blocks were associated with ADHD in the second sample. Six haplotypes within these blocks were also significantly (1.2 × 10-7 ≤ p ≤ .009) associated with ADHD in these samples. These risk variants were located in disease-related transposons and/or transcription-related functional regions. Major alleles of these risk variants significantly increased putamen volumes. Finally, KTN1 mRNA was significantly expressed in putamen across three independent cohorts. We concluded that the KTN1 variants were significantly associated with ADHD. KTN1 may play a functional role in the development of ADHD.

Dataset Information

Mitochondrial DNA haplogroups and risk of attention deficit and hyperactivity disorder in European Americans.

Publications

Mitochondrial DNA haplogroups and risk of attention deficit and hyperactivity disorder in European Americans.

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