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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; IJzendoorn, Marinus H. van; 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 and Sunyer, Jordi (2016): Heritability and Genome-Wide Association Analyses of Sleep Duration in Children: The EAGLE Consortium. In: Sleep, Vol. 39, No. 10: pp. 1859-1869

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Study Objectives: 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. Methods: 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. Results: We found evidence of significant but modest SNP heritability of sleep duration in children (SNP h(2) 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 (r(G) = 0.23, P = 0.05) between sleep duration in children and type 2 diabetes in adults, supporting the hypothesis of a common pathogenic mechanism. Conclusions: 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.

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