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 Estivill; David M Evans; Claudia Flexeder; Joan Fons; Juan R Gonzalez; Monica Guxens; Anke Huss; Marinus H van IJzendoorn; Vincent W V Jaddoe; 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

doi:10.5665/sleep.6170

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 Estivill, David M Evans, Claudia Flexeder, Joan Fons, Juan R Gonzalez, Monica Guxens, Anke Huss, Marinus H van IJzendoorn, Vincent W V JaddoeJordi 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 journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	1859-69
Number of pages	11
Journal	Sleep
Volume	39
Issue number	10
DOIs	https://doi.org/10.5665/sleep.6170
Publication status	Published - 19 Aug 2016

Keywords

SNP heritability
childhood sleep duration
genome-wide association study (GWAS)
meta-analysis
pathway analysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.5665/sleep.6170

HeritabilityFinal published version, 2.28 MBLicence: Taverne

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Marinelli, M., Pappa, I., Bustamante, M., Bonilla, C., Suarez, A., Tiesler, C. M., Vilor-Tejedor, N., Zafarmand, M. H., Alvarez-Pedrerol, M., Andersson, S., Bakermans-Kranenburg, M. J., Estivill, X., Evans, D. M., Flexeder, C., Fons, J., Gonzalez, J. R., Guxens, M., Huss, A., van IJzendoorn, M. H., ... Sunyer, J. (2016). Heritability and Genome-Wide Association Analyses of Sleep Duration in Children: The EAGLE Consortium. Sleep, 39(10), 1859-69. https://doi.org/10.5665/sleep.6170

@article{27d135457b2c41098909e1d0c32d164d,

title = "Heritability and Genome-Wide Association Analyses of Sleep Duration in Children: The EAGLE Consortium",

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.",

keywords = "SNP heritability, childhood sleep duration, genome-wide association study (GWAS), meta-analysis, pathway analysis",

author = "Marcella Marinelli and Irene Pappa and Mariona Bustamante and Carolina Bonilla and Anna Suarez and Tiesler, {Carla M} and Natalia Vilor-Tejedor and Zafarmand, {Mohammad Hadi} and Mar Alvarez-Pedrerol and Sture Andersson and Bakermans-Kranenburg, {Marian J} and Xavier Estivill and Evans, {David M} and Claudia Flexeder and Joan Fons and Gonzalez, {Juan R} and Monica Guxens and Anke Huss and {van IJzendoorn}, {Marinus H} and Jaddoe, {Vincent W V} and Jordi Julvez and Jari Lahti and M{\'o}nica L{\'o}pez-Vicente and Maria-Jose Lopez-Espinosa and Judith Manz and Mileva-Seitz, {Viara R} and Markus Perola and Anu-Katriina Pesonen and Fernando Rivadeneira and Salo, {Perttu P} and Shayan Shahand and Holger Schulz and Marie Standl and Elisabeth Thiering and Timpson, {Nicholas J} and Maties Torrent and Uitterlinden, {Andr{\'e} G} and Smith, {George Davey} and Marisa Estarlich and Joachim Heinrich and Katri R{\"a}ikk{\"o}nen and Vrijkotte, {Tanja G M} and Henning Tiemeier and Jordi Sunyer",

year = "2016",

month = aug,

day = "19",

doi = "10.5665/sleep.6170",

language = "English",

volume = "39",

pages = "1859--69",

journal = "Sleep",

issn = "0161-8105",

publisher = "Oxford University Press",

number = "10",

}

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, X, Evans, DM, Flexeder, C, Fons, J, Gonzalez, JR, Guxens, M, Huss, A, van IJzendoorn, MH, Jaddoe, VWV, Julvez, J, Lahti, J, López-Vicente, M, Lopez-Espinosa, M-J, Manz, J, Mileva-Seitz, VR, Perola, M, Pesonen, A-K, 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. 1859-69. https://doi.org/10.5665/sleep.6170

TY - JOUR

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

AU - Evans, David M

AU - Flexeder, Claudia

AU - Fons, 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 - 2016/8/19

Y1 - 2016/8/19

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 - SNP heritability

KW - childhood sleep duration

KW - genome-wide association study (GWAS)

KW - meta-analysis

KW - pathway analysis

U2 - 10.5665/sleep.6170

DO - 10.5665/sleep.6170

M3 - Article

C2 - 27568811

SN - 0161-8105

VL - 39

SP - 1859

EP - 1869

JO - Sleep

JF - Sleep

IS - 10

ER -

Heritability and Genome-Wide Association Analyses of Sleep Duration in Children: The EAGLE Consortium

Abstract

Keywords

UN SDGs

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