Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

Heming Wang; Jacqueline M. Lane; Samuel E. Jones; Hassan S. Dashti; Hanna M. Ollila; Andrew R. Wood; Vincent T. Van Hees; Ben Brumpton; Bendik S. Winsvold; Katri Kantojärvi; Teemu Palviainen; Brian E. Cade; Tamar Sofer; Yanwei Song; Krunal Patel; Simon G. Anderson; David A. Bechtold; Jack Bowden; Richard Emsley; Simon D. Kyle; Max A. Little; Andrew S. Loudon; Frank A. J. L. Scheer; Shaun M. Purcell; Rebecca C. Richmond; Kai Spiegelhalder; Jessica Tyrrell; Xiaofeng Zhu; Christer Hublin; Jaakko A. Kaprio; Kati Kristiansson; Sonja Sulkava; Tiina Paunio; Kristian Hveem; Jonas B. Nielsen; Cristen J. Willer; John-anker Zwart; Linn B. Strand; Timothy M. Frayling; David Ray; Deborah A. Lawlor; Martin K. Rutter; Michael N. Weedon; Susan Redline; Richa Saxena

doi:10.1038/s41467-019-11456-7

Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

Heming Wang, Jacqueline M. Lane, Samuel E. Jones, Hassan S. Dashti, Hanna M. Ollila, Andrew R. Wood, Vincent T. Van Hees, Ben Brumpton, Bendik S. Winsvold, Katri Kantojärvi, Teemu Palviainen, Brian E. Cade, Tamar Sofer, Yanwei Song, Krunal Patel, Simon G. Anderson, David A. Bechtold, Jack Bowden, Richard Emsley, Simon D. KyleMax A. Little, Andrew S. Loudon, Frank A. J. L. Scheer, Shaun M. Purcell, Rebecca C. Richmond, Kai Spiegelhalder, Jessica Tyrrell, Xiaofeng Zhu, Christer Hublin, Jaakko A. Kaprio, Kati Kristiansson, Sonja Sulkava, Tiina Paunio, Kristian Hveem, Jonas B. Nielsen, Cristen J. Willer, John-anker Zwart, Linn B. Strand, Timothy M. Frayling, David Ray, Deborah A. Lawlor, Martin K. Rutter, Michael N. Weedon, Susan Redline, Richa Saxena

College of Engineering and Physical Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

Excessive daytime sleepiness (EDS) affects 10–20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes - sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing.

Original language	English
Article number	3503
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-11456-7
Publication status	Published - 13 Aug 2019

Bibliographical note

© The Author(s) 2019. Open Access - This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The images or other third party
material in this article are included in the article’s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not included in the
article’s Creative Commons license and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this license, visit http://creativecommons.org/
licenses/by/4.0/.

Keywords

sleep
sleep disorders
genome-wide association

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10.1038/s41467-019-11456-7Licence: CC BY 3.0

Genome-wide association analysis of self-reported daytime sleepinessFinal published version, 1.52 MBLicence: CC BY 3.0

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Wang, H., Lane, J. M., Jones, S. E., Dashti, H. S., Ollila, H. M., Wood, A. R., Van Hees, V. T., Brumpton, B., Winsvold, B. S., Kantojärvi, K., Palviainen, T., Cade, B. E., Sofer, T., Song, Y., Patel, K., Anderson, S. G., Bechtold, D. A., Bowden, J., Emsley, R., ... Saxena, R. (2019). Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes. Nature Communications, 10(1), Article 3503. https://doi.org/10.1038/s41467-019-11456-7

@article{4acf1cbab1a2461fb53fc777be701448,

title = "Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes",

abstract = "Excessive daytime sleepiness (EDS) affects 10–20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes - sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing.",

keywords = "sleep, sleep disorders, genome-wide association",

author = "Heming Wang and Lane, {Jacqueline M.} and Jones, {Samuel E.} and Dashti, {Hassan S.} and Ollila, {Hanna M.} and Wood, {Andrew R.} and {Van Hees}, {Vincent T.} and Ben Brumpton and Winsvold, {Bendik S.} and Katri Kantoj{\"a}rvi and Teemu Palviainen and Cade, {Brian E.} and Tamar Sofer and Yanwei Song and Krunal Patel and Anderson, {Simon G.} and Bechtold, {David A.} and Jack Bowden and Richard Emsley and Kyle, {Simon D.} and Little, {Max A.} and Loudon, {Andrew S.} and Scheer, {Frank A. J. L.} and Purcell, {Shaun M.} and Richmond, {Rebecca C.} and Kai Spiegelhalder and Jessica Tyrrell and Xiaofeng Zhu and Christer Hublin and Kaprio, {Jaakko A.} and Kati Kristiansson and Sonja Sulkava and Tiina Paunio and Kristian Hveem and Nielsen, {Jonas B.} and Willer, {Cristen J.} and John-anker Zwart and Strand, {Linn B.} and Frayling, {Timothy M.} and David Ray and Lawlor, {Deborah A.} and Rutter, {Martin K.} and Weedon, {Michael N.} and Susan Redline and Richa Saxena",

note = "{\textcopyright} The Author(s) 2019. Open Access - This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article{\textquoteright}s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article{\textquoteright}s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.",

year = "2019",

month = aug,

day = "13",

doi = "10.1038/s41467-019-11456-7",

language = "English",

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journal = "Nature Communications",

issn = "2041-1723",

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Wang, H, Lane, JM, Jones, SE, Dashti, HS, Ollila, HM, Wood, AR, Van Hees, VT, Brumpton, B, Winsvold, BS, Kantojärvi, K, Palviainen, T, Cade, BE, Sofer, T, Song, Y, Patel, K, Anderson, SG, Bechtold, DA, Bowden, J, Emsley, R, Kyle, SD, Little, MA, Loudon, AS, Scheer, FAJL, Purcell, SM, Richmond, RC, Spiegelhalder, K, Tyrrell, J, Zhu, X, Hublin, C, Kaprio, JA, Kristiansson, K, Sulkava, S, Paunio, T, Hveem, K, Nielsen, JB, Willer, CJ, Zwart, J, Strand, LB, Frayling, TM, Ray, D, Lawlor, DA, Rutter, MK, Weedon, MN, Redline, S & Saxena, R 2019, 'Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes', Nature Communications, vol. 10, no. 1, 3503. https://doi.org/10.1038/s41467-019-11456-7

TY - JOUR

T1 - Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

AU - Wang, Heming

AU - Lane, Jacqueline M.

AU - Jones, Samuel E.

AU - Dashti, Hassan S.

AU - Ollila, Hanna M.

AU - Wood, Andrew R.

AU - Van Hees, Vincent T.

AU - Brumpton, Ben

AU - Winsvold, Bendik S.

AU - Kantojärvi, Katri

AU - Palviainen, Teemu

AU - Cade, Brian E.

AU - Sofer, Tamar

AU - Song, Yanwei

AU - Patel, Krunal

AU - Anderson, Simon G.

AU - Bechtold, David A.

AU - Bowden, Jack

AU - Emsley, Richard

AU - Kyle, Simon D.

AU - Little, Max A.

AU - Loudon, Andrew S.

AU - Scheer, Frank A. J. L.

AU - Purcell, Shaun M.

AU - Richmond, Rebecca C.

AU - Spiegelhalder, Kai

AU - Tyrrell, Jessica

AU - Zhu, Xiaofeng

AU - Hublin, Christer

AU - Kaprio, Jaakko A.

AU - Kristiansson, Kati

AU - Sulkava, Sonja

AU - Paunio, Tiina

AU - Hveem, Kristian

AU - Nielsen, Jonas B.

AU - Willer, Cristen J.

AU - Zwart, John-anker

AU - Strand, Linn B.

AU - Frayling, Timothy M.

AU - Ray, David

AU - Lawlor, Deborah A.

AU - Rutter, Martin K.

AU - Weedon, Michael N.

AU - Redline, Susan

AU - Saxena, Richa

N1 - © The Author(s) 2019. Open Access - This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.

PY - 2019/8/13

Y1 - 2019/8/13

N2 - Excessive daytime sleepiness (EDS) affects 10–20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes - sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing.

AB - Excessive daytime sleepiness (EDS) affects 10–20% of the population and is associated with substantial functional deficits. Here, we identify 42 loci for self-reported daytime sleepiness in GWAS of 452,071 individuals from the UK Biobank, with enrichment for genes expressed in brain tissues and in neuronal transmission pathways. We confirm the aggregate effect of a genetic risk score of 42 SNPs on daytime sleepiness in independent Scandinavian cohorts and on other sleep disorders (restless legs syndrome, insomnia) and sleep traits (duration, chronotype, accelerometer-derived sleep efficiency and daytime naps or inactivity). However, individual daytime sleepiness signals vary in their associations with objective short vs long sleep, and with markers of sleep continuity. The 42 sleepiness variants primarily cluster into two predominant composite biological subtypes - sleep propensity and sleep fragmentation. Shared genetic links are also seen with obesity, coronary heart disease, psychiatric diseases, cognitive traits and reproductive ageing.

KW - sleep

KW - sleep disorders

KW - genome-wide association

UR - http://www.nature.com/articles/s41467-019-11456-7

UR - http://www.scopus.com/inward/record.url?scp=85070777691&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-11456-7

DO - 10.1038/s41467-019-11456-7

M3 - Article

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 3503

ER -

Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

Abstract

Bibliographical note

Keywords

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