Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

Hassan S. Dashti; Samuel E. Jones; Andrew R. Wood; Jacqueline M. Lane; Vincent T. Van Hees; Heming Wang; Jessica A. Rhodes; Yanwei Song; Krunal Patel; Simon G. Anderson; Robin N. Beaumont; David A. Bechtold; Jack Bowden; Brian E. Cade; Marta Garaulet; Simon D. Kyle; Max A. Little; Andrew S. Loudon; Annemarie I. Luik; Frank A. J. L. Scheer; Kai Spiegelhalder; Jessica Tyrrell; Daniel J. Gottlieb; Henning Tiemeier; David W. Ray; Shaun M. Purcell; Timothy M. Frayling; Susan Redline; Deborah A. Lawlor; Martin K. Rutter; Michael N. Weedon; Richa Saxena

doi:10.1038/s41467-019-08917-4

Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

Hassan S. Dashti, Samuel E. Jones, Andrew R. Wood, Jacqueline M. Lane, Vincent T. Van Hees, Heming Wang, Jessica A. Rhodes, Yanwei Song, Krunal Patel, Simon G. Anderson, Robin N. Beaumont, David A. Bechtold, Jack Bowden, Brian E. Cade, Marta Garaulet, Simon D. Kyle, Max A. Little, Andrew S. Loudon, Annemarie I. Luik, Frank A. J. L. ScheerKai Spiegelhalder, Jessica Tyrrell, Daniel J. Gottlieb, Henning Tiemeier, David W. Ray, Shaun M. Purcell, Timothy M. Frayling, Susan Redline, Deborah A. Lawlor, Martin K. Rutter, Michael N. Weedon, Richa Saxena

Computer Science

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Abstract

Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration (p < 5 × 10⁻⁸; 43 loci at p < 6 × 10⁻⁹). Replication is observed for PAX8, VRK2, and FBXL12/UBL5/PIN1 loci in the CHARGE study (n = 47,180; p < 6.3 × 10⁻⁴), and 55 signals show sign-concordant effects. The 78 loci further associate with accelerometer-derived sleep duration, daytime inactivity, sleep efficiency and number of sleep bouts in secondary analysis (n = 85,499). Loci are enriched for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission and plasticity, among others. Genetic correlation indicates shared links with anthropometric, cognitive, metabolic, and psychiatric traits and two-sample Mendelian randomization highlights a bidirectional causal link with schizophrenia. This work provides insights into the genetic basis for inter-individual variation in sleep duration implicating multiple biological pathways.

Original language	English
Article number	1100
Number of pages	12
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-08917-4
Publication status	Published - 7 Mar 2019

Keywords

Accelerometry
Adult
Aged
European Continental Ancestry Group
Female
Genetic Loci
Genome-Wide Association Study
Humans
Linkage Disequilibrium
Male
Middle Aged
Polymorphism, Single Nucleotide
Schizophrenia/genetics
Self Report
Sleep/genetics
United Kingdom

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Dashti_et_al_Genome_wide_association_study_identifies_genetic_loci_for_self_reported_habitual_sleep_duration_Nature_Communications_2019
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Dashti, H. S., Jones, S. E., Wood, A. R., Lane, J. M., Van Hees, V. T., Wang, H., Rhodes, J. A., Song, Y., Patel, K., Anderson, S. G., Beaumont, R. N., Bechtold, D. A., Bowden, J., Cade, B. E., Garaulet, M., Kyle, S. D., Little, M. A., Loudon, A. S., Luik, A. I., ... Saxena, R. (2019). Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates. Nature Communications, 10(1), Article 1100. https://doi.org/10.1038/s41467-019-08917-4

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title = "Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates",

abstract = "Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration (p < 5 × 10−8; 43 loci at p < 6 × 10−9). Replication is observed for PAX8, VRK2, and FBXL12/UBL5/PIN1 loci in the CHARGE study (n = 47,180; p < 6.3 × 10−4), and 55 signals show sign-concordant effects. The 78 loci further associate with accelerometer-derived sleep duration, daytime inactivity, sleep efficiency and number of sleep bouts in secondary analysis (n = 85,499). Loci are enriched for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission and plasticity, among others. Genetic correlation indicates shared links with anthropometric, cognitive, metabolic, and psychiatric traits and two-sample Mendelian randomization highlights a bidirectional causal link with schizophrenia. This work provides insights into the genetic basis for inter-individual variation in sleep duration implicating multiple biological pathways.",

keywords = "Accelerometry, Adult, Aged, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Schizophrenia/genetics, Self Report, Sleep/genetics, United Kingdom",

author = "Dashti, {Hassan S.} and Jones, {Samuel E.} and Wood, {Andrew R.} and Lane, {Jacqueline M.} and {Van Hees}, {Vincent T.} and Heming Wang and Rhodes, {Jessica A.} and Yanwei Song and Krunal Patel and Anderson, {Simon G.} and Beaumont, {Robin N.} and Bechtold, {David A.} and Jack Bowden and Cade, {Brian E.} and Marta Garaulet and Kyle, {Simon D.} and Little, {Max A.} and Loudon, {Andrew S.} and Luik, {Annemarie I.} and Scheer, {Frank A. J. L.} and Kai Spiegelhalder and Jessica Tyrrell and Gottlieb, {Daniel J.} and Henning Tiemeier and Ray, {David W.} and Purcell, {Shaun M.} and Frayling, {Timothy M.} and Susan Redline and Lawlor, {Deborah A.} and Rutter, {Martin K.} and Weedon, {Michael N.} and Richa Saxena",

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doi = "10.1038/s41467-019-08917-4",

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Dashti, HS, Jones, SE, Wood, AR, Lane, JM, Van Hees, VT, Wang, H, Rhodes, JA, Song, Y, Patel, K, Anderson, SG, Beaumont, RN, Bechtold, DA, Bowden, J, Cade, BE, Garaulet, M, Kyle, SD, Little, MA, Loudon, AS, Luik, AI, Scheer, FAJL, Spiegelhalder, K, Tyrrell, J, Gottlieb, DJ, Tiemeier, H, Ray, DW, Purcell, SM, Frayling, TM, Redline, S, Lawlor, DA, Rutter, MK, Weedon, MN & Saxena, R 2019, 'Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates', Nature Communications, vol. 10, no. 1, 1100. https://doi.org/10.1038/s41467-019-08917-4

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T1 - Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

AU - Dashti, Hassan S.

AU - Jones, Samuel E.

AU - Wood, Andrew R.

AU - Lane, Jacqueline M.

AU - Van Hees, Vincent T.

AU - Wang, Heming

AU - Rhodes, Jessica A.

AU - Song, Yanwei

AU - Patel, Krunal

AU - Anderson, Simon G.

AU - Beaumont, Robin N.

AU - Bechtold, David A.

AU - Bowden, Jack

AU - Cade, Brian E.

AU - Garaulet, Marta

AU - Kyle, Simon D.

AU - Little, Max A.

AU - Loudon, Andrew S.

AU - Luik, Annemarie I.

AU - Scheer, Frank A. J. L.

AU - Spiegelhalder, Kai

AU - Tyrrell, Jessica

AU - Gottlieb, Daniel J.

AU - Tiemeier, Henning

AU - Ray, David W.

AU - Purcell, Shaun M.

AU - Frayling, Timothy M.

AU - Redline, Susan

AU - Lawlor, Deborah A.

AU - Rutter, Martin K.

AU - Weedon, Michael N.

AU - Saxena, Richa

PY - 2019/3/7

Y1 - 2019/3/7

N2 - Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration (p < 5 × 10−8; 43 loci at p < 6 × 10−9). Replication is observed for PAX8, VRK2, and FBXL12/UBL5/PIN1 loci in the CHARGE study (n = 47,180; p < 6.3 × 10−4), and 55 signals show sign-concordant effects. The 78 loci further associate with accelerometer-derived sleep duration, daytime inactivity, sleep efficiency and number of sleep bouts in secondary analysis (n = 85,499). Loci are enriched for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission and plasticity, among others. Genetic correlation indicates shared links with anthropometric, cognitive, metabolic, and psychiatric traits and two-sample Mendelian randomization highlights a bidirectional causal link with schizophrenia. This work provides insights into the genetic basis for inter-individual variation in sleep duration implicating multiple biological pathways.

AB - Sleep is an essential state of decreased activity and alertness but molecular factors regulating sleep duration remain unknown. Through genome-wide association analysis in 446,118 adults of European ancestry from the UK Biobank, we identify 78 loci for self-reported habitual sleep duration (p < 5 × 10−8; 43 loci at p < 6 × 10−9). Replication is observed for PAX8, VRK2, and FBXL12/UBL5/PIN1 loci in the CHARGE study (n = 47,180; p < 6.3 × 10−4), and 55 signals show sign-concordant effects. The 78 loci further associate with accelerometer-derived sleep duration, daytime inactivity, sleep efficiency and number of sleep bouts in secondary analysis (n = 85,499). Loci are enriched for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission and plasticity, among others. Genetic correlation indicates shared links with anthropometric, cognitive, metabolic, and psychiatric traits and two-sample Mendelian randomization highlights a bidirectional causal link with schizophrenia. This work provides insights into the genetic basis for inter-individual variation in sleep duration implicating multiple biological pathways.

KW - Accelerometry

KW - Adult

KW - Aged

KW - European Continental Ancestry Group

KW - Female

KW - Genetic Loci

KW - Genome-Wide Association Study

KW - Humans

KW - Linkage Disequilibrium

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Schizophrenia/genetics

KW - Self Report

KW - Sleep/genetics

KW - United Kingdom

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DO - 10.1038/s41467-019-08917-4

M3 - Article

C2 - 30846698

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1100

ER -

Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

Abstract

Keywords

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