Marinelli Marcella, Pappa Irene, Bustamante Mariona, Bonilla Carolina, Suarez Anna, Tiesler Carla M, Vilor-Tejedor Natalia, Zafarmand Mohammad Hadi, Alvarez-Pedrerol Mar, Andersson Sture, Bakermans-Kranenburg Marian J, Estivill Xavier, Evans David M, Flexeder Claudia, Forns Joan, Gonzalez Juan R, Guxens Monica, Huss Anke, van IJzendoorn Marinus H, Jaddoe Vincent W V, Julvez Jordi, Lahti Jari, López-Vicente Mónica, Lopez-Espinosa Maria-Jose, Manz Judith, Mileva-Seitz Viara R, Perola Markus, Pesonen Anu-Katriina, Rivadeneira Fernando, Salo Perttu P, Shahand Shayan, Schulz Holger, Standl Marie, Thiering Elisabeth, Timpson Nicholas J, Torrent Maties, Uitterlinden André G, Smith George Davey, Estarlich Marisa, Heinrich Joachim, Räikkönen Katri, Vrijkotte Tanja G M, Tiemeier Henning, Sunyer Jordi
Agency for Healthcare Quality and Evaluation of Catalonia (AQuAS), Roc Boronat, Barcelona, Spain.
Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Sleep. 2016 Oct 1;39(10):1859-1869. doi: 10.5665/sleep.6170.
Low or excessive sleep duration has been associated with multiple outcomes, but the biology behind these associations remains elusive. Specifically, genetic studies in children are scarce. In this study, we aimed to: (1) estimate the proportion of genetic variance of sleep duration in children attributed to common single nucleotide polymorphisms (SNPs), (2) identify novel SNPs associated with sleep duration in children, and (3) investigate the genetic overlap of sleep duration in children and related metabolic and psychiatric traits.
We performed a population-based molecular genetic study, using data form the EArly Genetics and Life course Epidemiology (EAGLE) Consortium. 10,554 children of European ancestry were included in the discovery, and 1,250 children in the replication phase.
We found evidence of significant but modest SNP heritability of sleep duration in children (SNP 0.14, 95% CI [0.05, 0.23]) using the LD score regression method. A novel region at chromosome 11q13.4 (top SNP: rs74506765, P = 2.27e-08) was associated with sleep duration in children, but this was not replicated in independent studies. Nominally significant genetic overlap was only found ( = 0.23, P = 0.05) between sleep duration in children and type 2 diabetes in adults, supporting the hypothesis of a common pathogenic mechanism.
The significant SNP heritability of sleep duration in children and the suggestive genetic overlap with type 2 diabetes support the search for genetic mechanisms linking sleep duration in children to multiple outcomes in health and disease.
睡眠时间过短或过长与多种结局相关,但这些关联背后的生物学机制仍不清楚。具体而言,关于儿童的遗传学研究较少。在本研究中,我们旨在:(1)估计儿童睡眠时间遗传变异中归因于常见单核苷酸多态性(SNP)的比例,(2)识别与儿童睡眠时间相关的新SNP,以及(3)研究儿童睡眠时间与相关代谢和精神特质之间的遗传重叠。
我们利用早期遗传学与生命历程流行病学(EAGLE)联盟的数据进行了一项基于人群的分子遗传学研究。发现阶段纳入了10554名欧洲血统儿童,复制阶段纳入了1250名儿童。
我们使用连锁不平衡评分回归方法发现儿童睡眠时间存在显著但适度的SNP遗传力证据(SNP h² = 0.14,95%CI [0.05, 0.23])。11号染色体q13.4区域的一个新位点(顶级SNP:rs74506765,P = 2.27e - 08)与儿童睡眠时间相关,但在独立研究中未得到复制。仅在儿童睡眠时间与成人2型糖尿病之间发现了名义上显著的遗传重叠(r = 0.23,P = 0.05),支持了共同致病机制的假设。
儿童睡眠时间显著的SNP遗传力以及与2型糖尿病提示性的遗传重叠支持寻找将儿童睡眠时间与健康和疾病中的多种结局联系起来的遗传机制。