Heritability and genome-wide association analyses of sleep duration in children

The EAGLE consortium

Marcella Marinelli, Irene Pappa, Mariona Bustamante, Carolina Bonilla, Anna Suarez, Carla M. Tiesler, Natalia Vilor-Tejedor, Mohammad Hadi Zafarmand, Mar Alvarez-Pedrerol, Sture Andersson, Marian J. Bakermans-Kranenburg, Xavier P. Estivill, David M. Evans, Claudia Flexeder, Joan Forns, Juan R. Gonzalez, Monica Guxens, Anke Huss, Marinus H. Van Ijzendoorn, Vincent W V Jaddoe & 24 others Jordi Julvez, Jari Lahti, Mónica López-Vicente, Maria Jose Lopez-Espinosa, Judith Manz, Viara R. Mileva-Seitz, Markus Perola, Anu Katriina Pesonen, Fernando Rivadeneira, Perttu P. Salo, Shayan Shahand, Holger Schulz, Marie Standl, Elisabeth Thiering, Nicholas J. Timpson, Maties Torrent, André G. Uitterlinden, George Davey Smith, Marisa Estarlich, Joachim Heinrich, Katri Räikkönen, Tanja G M Vrijkotte, Henning Tiemeier, Jordi Sunyer

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 h2 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 (rG = 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.

Original languageEnglish
Pages (from-to)1859-1869
Number of pages11
JournalSleep
Volume39
Issue number10
DOIs
Publication statusPublished - 1 Oct 2016
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Sleep
Epidemiology
Single Nucleotide Polymorphism
Type 2 Diabetes Mellitus
Psychiatry
Molecular Biology
Chromosomes

Keywords

  • Childhood sleep duration
  • Genome-wide association study (GWAS)
  • Meta-analysis
  • Pathway analysis
  • SNP heritability

ASJC Scopus subject areas

  • Clinical Neurology
  • Physiology (medical)

Cite this

Marinelli, M., Pappa, I., Bustamante, M., Bonilla, C., Suarez, A., Tiesler, C. M., ... Sunyer, J. (2016). Heritability and genome-wide association analyses of sleep duration in children: The EAGLE consortium. Sleep, 39(10), 1859-1869. https://doi.org/10.5665/sleep.6170

Heritability and genome-wide association analyses of sleep duration in children : The EAGLE consortium. / 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 P.; 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.

In: Sleep, Vol. 39, No. 10, 01.10.2016, p. 1859-1869.

Research output: Contribution to journalArticle

Marinelli, M, Pappa, I, Bustamante, M, Bonilla, C, Suarez, A, Tiesler, CM, Vilor-Tejedor, N, Zafarmand, MH, Alvarez-Pedrerol, M, Andersson, S, Bakermans-Kranenburg, MJ, Estivill, XP, Evans, DM, Flexeder, C, Forns, J, Gonzalez, JR, Guxens, M, Huss, A, Van Ijzendoorn, MH, Jaddoe, VWV, Julvez, J, Lahti, J, López-Vicente, M, Lopez-Espinosa, MJ, Manz, J, Mileva-Seitz, VR, Perola, M, Pesonen, AK, Rivadeneira, F, Salo, PP, Shahand, S, Schulz, H, Standl, M, Thiering, E, Timpson, NJ, Torrent, M, Uitterlinden, AG, Smith, GD, Estarlich, M, Heinrich, J, Räikkönen, K, Vrijkotte, TGM, Tiemeier, H & Sunyer, J 2016, 'Heritability and genome-wide association analyses of sleep duration in children: The EAGLE consortium', Sleep, vol. 39, no. 10, pp. 1859-1869. https://doi.org/10.5665/sleep.6170
Marinelli M, Pappa I, Bustamante M, Bonilla C, Suarez A, Tiesler CM et al. Heritability and genome-wide association analyses of sleep duration in children: The EAGLE consortium. Sleep. 2016 Oct 1;39(10):1859-1869. https://doi.org/10.5665/sleep.6170
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 P. ; 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. / Heritability and genome-wide association analyses of sleep duration in children : The EAGLE consortium. In: Sleep. 2016 ; Vol. 39, No. 10. pp. 1859-1869.
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abstract = "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 h2 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 (rG = 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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T1 - Heritability and genome-wide association analyses of sleep duration in children

T2 - The EAGLE consortium

AU - Marinelli, Marcella

AU - Pappa, Irene

AU - Bustamante, Mariona

AU - Bonilla, Carolina

AU - Suarez, Anna

AU - Tiesler, Carla M.

AU - Vilor-Tejedor, Natalia

AU - Zafarmand, Mohammad Hadi

AU - Alvarez-Pedrerol, Mar

AU - Andersson, Sture

AU - Bakermans-Kranenburg, Marian J.

AU - Estivill, Xavier P.

AU - Evans, David M.

AU - Flexeder, Claudia

AU - Forns, Joan

AU - Gonzalez, Juan R.

AU - Guxens, Monica

AU - Huss, Anke

AU - Van Ijzendoorn, Marinus H.

AU - Jaddoe, Vincent W V

AU - Julvez, Jordi

AU - Lahti, Jari

AU - López-Vicente, Mónica

AU - Lopez-Espinosa, Maria Jose

AU - Manz, Judith

AU - Mileva-Seitz, Viara R.

AU - Perola, Markus

AU - Pesonen, Anu Katriina

AU - Rivadeneira, Fernando

AU - Salo, Perttu P.

AU - Shahand, Shayan

AU - Schulz, Holger

AU - Standl, Marie

AU - Thiering, Elisabeth

AU - Timpson, Nicholas J.

AU - Torrent, Maties

AU - Uitterlinden, André G.

AU - Smith, George Davey

AU - Estarlich, Marisa

AU - Heinrich, Joachim

AU - Räikkönen, Katri

AU - Vrijkotte, Tanja G M

AU - Tiemeier, Henning

AU - Sunyer, Jordi

PY - 2016/10/1

Y1 - 2016/10/1

N2 - 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 h2 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 (rG = 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.

AB - 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 h2 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 (rG = 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.

KW - Childhood sleep duration

KW - Genome-wide association study (GWAS)

KW - Meta-analysis

KW - Pathway analysis

KW - SNP heritability

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