KTN1 variants and risk for attention deficit hyperactivity disorder
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Le résumé fourni par la source
Abstract 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.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- <scp><i>KTN1</i></scp> variants and risk for attention deficit hyperactivity disorder
- Date Crossref
- 19/03/2020
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Yale University Department of Psychiatry pays non établi dans la noticeUniversité ou école supérieure
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Beijing HuiLongGuan Hospital pays non établi dans la noticeÉtablissement de santé
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Shanghai Mental Health Center pays non établi dans la noticeÉtablissement de santé
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Tianjin Anding Hospital pays non établi dans la noticeÉtablissement de santé
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Fujian Medical University Department of Psychiatry pays non établi dans la noticeUniversité ou école supérieure
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Fuzhou Pulmonary Hospital of Fujian pays non établi dans la noticeÉtablissement de santé
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Fuzhou Neuro Psychiatric Hospital pays non établi dans la noticeÉtablissement de santé
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Shanghai Jiao Tong University Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
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Tongren Hospital pays non établi dans la noticeÉtablissement de santé
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Zhuhai People's Hospital pays non établi dans la noticeÉtablissement de santé
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Weihai Maternal and Child Health Hospital pays non établi dans la noticeÉtablissement de santé
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First Affiliated Hospital of Fujian Medical University pays non établi dans la noticeÉtablissement de santé
Department of Psychiatry — Yale University, Beijing HuiLongGuan Hospital et Shanghai Mental Health Center, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.