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钙电压门控通道亚基α1 C基因(CACNA1C)的变异与婴儿的睡眠潜伏期有关。

Variants in calcium voltage-gated channel subunit Alpha1 C-gene (CACNA1C) are associated with sleep latency in infants.

作者信息

Kantojärvi Katri, Liuhanen Johanna, Saarenpää-Heikkilä Outi, Satomaa Anna-Liisa, Kylliäinen Anneli, Pölkki Pirjo, Jaatela Julia, Toivola Auli, Milani Lili, Himanen Sari-Leena, Porkka-Heiskanen Tarja, Paavonen Juulia, Paunio Tiina

机构信息

Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland.

Department of Psychiatry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

出版信息

PLoS One. 2017 Aug 9;12(8):e0180652. doi: 10.1371/journal.pone.0180652. eCollection 2017.

Abstract

Genetic variants in CACNA1C (calcium voltage-gated channel subunit alpha1 C) are associated with bipolar disorder and schizophrenia where sleep disturbances are common. In an experimental model, Cacna1c has been found to modulate the electrophysiological architecture of sleep. There are strong genetic influences for consolidation of sleep in infancy, but only a few studies have thus far researched the genetic factors underlying the process. We hypothesized that genetic variants in CACNA1C affect the regulation of sleep in early development. Seven variants that were earlier associated (genome-wide significantly) with psychiatric disorders at CACNA1C were selected for analyses. The study sample consists of 1086 infants (520 girls and 566 boys) from the Finnish CHILD-SLEEP birth cohort (genotyped by Illumina Infinium PsychArray BeadChip). Sleep length, latency, and nightly awakenings were reported by the parents of the infants with a home-delivered questionnaire at 8 months of age. The genetic influence of CACNA1C variants on sleep in infants was examined by using PLINK software. Three of the examined CACNA1C variants, rs4765913, rs4765914, and rs2239063, were associated with sleep latency (permuted P<0.05). There was no significant association between studied variants and night awakenings or sleep duration. CACNA1C variants for psychiatric disorders were found to be associated with long sleep latency among 8-month-old infants. It remains to be clarified whether the findings refer to defective regulation of sleep, or to distractibility of sleep under external influences.

摘要

CACNA1C(钙电压门控通道亚基α1 C)基因变异与双相情感障碍和精神分裂症相关,而睡眠障碍在这些疾病中很常见。在一个实验模型中,已发现Cacna1c可调节睡眠的电生理结构。婴儿期睡眠巩固存在强大的遗传影响,但迄今为止只有少数研究探讨了这一过程背后的遗传因素。我们假设CACNA1C基因变异会影响早期发育阶段的睡眠调节。选择了七个先前在CACNA1C基因处与精神疾病相关(全基因组显著相关)的变异进行分析。研究样本包括来自芬兰儿童睡眠出生队列的1086名婴儿(520名女孩和566名男孩)(通过Illumina Infinium PsychArray BeadChip进行基因分型)。婴儿的父母在婴儿8个月大时通过家庭送达的问卷报告了睡眠时间、入睡潜伏期和夜间觉醒情况。使用PLINK软件检查了CACNA1C变异对婴儿睡眠的遗传影响。所检查的三个CACNA1C变异,即rs4765913、rs4765914和rs2239063,与入睡潜伏期相关(置换P<0.05)。所研究的变异与夜间觉醒或睡眠时间之间没有显著关联。发现与精神疾病相关的CACNA1C变异与8个月大婴儿的长入睡潜伏期有关。这些发现是指睡眠调节缺陷还是指外部影响下睡眠的易分散性,仍有待阐明。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba26/5549883/243b6aa5cbea/pone.0180652.g001.jpg

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