KCNJ6 variants modulate reward-related brain processes and impact executive functions in attention-deficit/hyperactivity disorder
Ziegler G. C., Röser C., Renner T., Hahn T., Ehlis A. -., Weber H., Dempfle A., Walitza S., Jacob C., Romanos M., Fallgatter A. J., Reif A., Lesh K. Yu.
American Journal of Medical Genetics. Part B. Neuropsychiatric genetics
Vol.183, Issue5, P. 247-257
Опубликовано: 2020
Тип ресурса: Статья
Аннотация:
KCNJ6, encoding a potassium channel subunit, regulates the excitability of dopaminergic neurons and is expressed in attention-deficit/hyperactivity disorder (ADHD)-relevant brain regions. As a potential ADHD risk gene, KCNJ6, therefore, may contribute to the endophenotypic variation of the disorder. The impact of two SNPs, rs7275707 and rs6517442, both located in the transcriptional control region of KCNJ6, on reporter gene expression was explored in cultured cells. The KCNJ6 variants were then tested for association with ADHD and personality traits in a family-based sample (165 affected children) and an adult case–control sample (450 patients, 426 controls). Furthermore, the genotypic influence on performance in an n-back task and a cued continuous performance test (cCPT) was investigated by electroencephalography recordings. Finally, rs6517442 function was assessed by a reward anticipation paradigm using functional magnetic resonance imaging. Different haplotypes of rs7275707 and rs6
Ключевые слова:
ADHD; dopamine; executive functions; KCNJ6; reward
potassium channel; potassium channel KCNJ6; unclassified drug; adult; Article; attention deficit disorder; child; controlled study; disease association; electroencephalogram; electroencephalography; electrophysiology; endophenotype; executive function; functional magnetic resonance imaging; gene; gene expression; gene locus; genetic association; genetic database; genetic trait; genetic transfection; genetic variability; genotype; haplotype; human; KCNJ6 gene; luciferase assay; major clinical study; mutagenesis; neuroimaging; priority journal; promoter region; reward; risk factor; single nucleotide polymorphism; transcription regulation; working memory
Язык текста: Английский
ISSN: 1552-485X
Ziegler G. C.
Röser C.
Renner T.
Hahn T.
Ehlis A. -. A.-C.
Weber H.
Dempfle A.
Walitza S.
Jacob C.
Romanos M.
Fallgatter A. J.
Reif A.
Lesh K. Yu. Klaus-Peter Yulius 1957-
Зиеглер Г. C.
Рöсер C.
Реннер Т.
Хахн Т.
Ехлис А. -. А.-C.
Wебер Х.
Демпфле А.
Wалитза С.
Йаcоб C.
Романос М.
Фаллгаттер А. Й.
Реиф А.
Леш К. Ю. Клаус-Петер Юлиус 1957-
KCNJ6 variants modulate reward-related brain processes and impact executive functions in attention-deficit/hyperactivity disorder
Текст визуальный непосредственный
American Journal of Medical Genetics. Part B. Neuropsychiatric genetics
Wiley-Liss Inc
Vol.183, Issue5 P. 247-257
2020
Статья
ADHD dopamine executive functions KCNJ6 reward
potassium channel potassium channel KCNJ6 unclassified drug adult Article attention deficit disorder child controlled study disease association electroencephalogram electroencephalography electrophysiology endophenotype executive function functional magnetic resonance imaging gene gene expression gene locus genetic association genetic database genetic trait genetic transfection genetic variability genotype haplotype human KCNJ6 gene luciferase assay major clinical study mutagenesis neuroimaging priority journal promoter region reward risk factor single nucleotide polymorphism transcription regulation working memory
KCNJ6, encoding a potassium channel subunit, regulates the excitability of dopaminergic neurons and is expressed in attention-deficit/hyperactivity disorder (ADHD)-relevant brain regions. As a potential ADHD risk gene, KCNJ6, therefore, may contribute to the endophenotypic variation of the disorder. The impact of two SNPs, rs7275707 and rs6517442, both located in the transcriptional control region of KCNJ6, on reporter gene expression was explored in cultured cells. The KCNJ6 variants were then tested for association with ADHD and personality traits in a family-based sample (165 affected children) and an adult case–control sample (450 patients, 426 controls). Furthermore, the genotypic influence on performance in an n-back task and a cued continuous performance test (cCPT) was investigated by electroencephalography recordings. Finally, rs6517442 function was assessed by a reward anticipation paradigm using functional magnetic resonance imaging. Different haplotypes of rs7275707 and rs6