Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits

Jacqueline M. Lane, Jingjing Liang, Irma Vlasac, Simon G. Anderson, David A. Bechtold, Jack Bowden, Richard Emsley, Shubhroz Gill, Max A Little, Annemarie I. Luik, Andrew Loudon, Frank A.J.L. Scheer, Shaun M. Purcell, Simon D. Kyle, Deborah A. Lawlor, Xiaofeng Zhu, Susan Redline, David W. Ray, Martin K. Rutter, Richa Saxena

Research output: Contribution to journalLetter

Abstract

Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30% of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586). We discover loci associated with insomnia symptoms (near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR-OPHN1) and a composite sleep trait (near PATJ (INADL) and HCRTR2) and replicate a locus associated with sleep duration (at PAX8). We also observe genetic correlation between longer sleep duration and schizophrenia risk (rg = 0.29, P = 1.90 × 10(-13)) and between increased levels of excessive daytime sleepiness and increased measures for adiposity traits (body mass index (BMI): rg = 0.20, P = 3.12 × 10(-9); waist circumference: rg = 0.20, P = 2.12 × 10(-7)).

Original languageEnglish
Pages (from-to)274 - 281
Number of pages8
JournalNature Genetics
Volume49
Issue number2
Early online date19 Dec 2016
DOIs
Publication statusPublished - Feb 2017

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Genome-Wide Association Study
Sleep
Sleep Initiation and Maintenance Disorders
Adiposity
Waist Circumference
Psychiatry
Schizophrenia
Body Mass Index
Mortality
Genes

Cite this

Lane, J. M., Liang, J., Vlasac, I., Anderson, S. G., Bechtold, D. A., Bowden, J., ... Saxena, R. (2017). Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits. Nature Genetics, 49(2), 274 - 281. https://doi.org/10.1038/ng.3749
Lane, Jacqueline M. ; Liang, Jingjing ; Vlasac, Irma ; Anderson, Simon G. ; Bechtold, David A. ; Bowden, Jack ; Emsley, Richard ; Gill, Shubhroz ; Little, Max A ; Luik, Annemarie I. ; Loudon, Andrew ; Scheer, Frank A.J.L. ; Purcell, Shaun M. ; Kyle, Simon D. ; Lawlor, Deborah A. ; Zhu, Xiaofeng ; Redline, Susan ; Ray, David W. ; Rutter, Martin K. ; Saxena, Richa. / Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits. In: Nature Genetics. 2017 ; Vol. 49, No. 2. pp. 274 - 281.
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abstract = "Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30{\%} of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586). We discover loci associated with insomnia symptoms (near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR-OPHN1) and a composite sleep trait (near PATJ (INADL) and HCRTR2) and replicate a locus associated with sleep duration (at PAX8). We also observe genetic correlation between longer sleep duration and schizophrenia risk (rg = 0.29, P = 1.90 × 10(-13)) and between increased levels of excessive daytime sleepiness and increased measures for adiposity traits (body mass index (BMI): rg = 0.20, P = 3.12 × 10(-9); waist circumference: rg = 0.20, P = 2.12 × 10(-7)).",
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Lane, JM, Liang, J, Vlasac, I, Anderson, SG, Bechtold, DA, Bowden, J, Emsley, R, Gill, S, Little, MA, Luik, AI, Loudon, A, Scheer, FAJL, Purcell, SM, Kyle, SD, Lawlor, DA, Zhu, X, Redline, S, Ray, DW, Rutter, MK & Saxena, R 2017, 'Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits', Nature Genetics, vol. 49, no. 2, pp. 274 - 281. https://doi.org/10.1038/ng.3749

Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits. / Lane, Jacqueline M.; Liang, Jingjing; Vlasac, Irma; Anderson, Simon G.; Bechtold, David A.; Bowden, Jack; Emsley, Richard; Gill, Shubhroz; Little, Max A; Luik, Annemarie I.; Loudon, Andrew; Scheer, Frank A.J.L.; Purcell, Shaun M.; Kyle, Simon D.; Lawlor, Deborah A.; Zhu, Xiaofeng; Redline, Susan; Ray, David W.; Rutter, Martin K.; Saxena, Richa.

In: Nature Genetics, Vol. 49, No. 2, 02.2017, p. 274 - 281.

Research output: Contribution to journalLetter

TY - JOUR

T1 - Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits

AU - Lane, Jacqueline M.

AU - Liang, Jingjing

AU - Vlasac, Irma

AU - Anderson, Simon G.

AU - Bechtold, David A.

AU - Bowden, Jack

AU - Emsley, Richard

AU - Gill, Shubhroz

AU - Little, Max A

AU - Luik, Annemarie I.

AU - Loudon, Andrew

AU - Scheer, Frank A.J.L.

AU - Purcell, Shaun M.

AU - Kyle, Simon D.

AU - Lawlor, Deborah A.

AU - Zhu, Xiaofeng

AU - Redline, Susan

AU - Ray, David W.

AU - Rutter, Martin K.

AU - Saxena, Richa

PY - 2017/2

Y1 - 2017/2

N2 - Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25-30% of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586). We discover loci associated with insomnia symptoms (near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR-OPHN1) and a composite sleep trait (near PATJ (INADL) and HCRTR2) and replicate a locus associated with sleep duration (at PAX8). We also observe genetic correlation between longer sleep duration and schizophrenia risk (rg = 0.29, P = 1.90 × 10(-13)) and between increased levels of excessive daytime sleepiness and increased measures for adiposity traits (body mass index (BMI): rg = 0.20, P = 3.12 × 10(-9); waist circumference: rg = 0.20, P = 2.12 × 10(-7)).

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