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

doi:10.1038/ng.3749

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 journal › Letter, comment/opinion or interview › peer-review

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 language	English
Pages (from-to)	274 - 281
Number of pages	8
Journal	Nature Genetics
Volume	49
Issue number	2
Early online date	19 Dec 2016
DOIs	https://doi.org/10.1038/ng.3749
Publication status	Published - Feb 2017

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Lane, J. M., Liang, J., Vlasac, I., Anderson, S. G., Bechtold, D. A., Bowden, J., Emsley, R., Gill, S., Little, M. A., Luik, A. I., Loudon, A., Scheer, F. A. J. L., Purcell, S. M., Kyle, S. D., Lawlor, D. A., Zhu, X., Redline, S., Ray, D. W., Rutter, M. K., & 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

@article{3b72a58e6a3b41308e52c92ccd4f9bcd,

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

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)).",

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

year = "2017",

month = feb,

doi = "10.1038/ng.3749",

language = "English",

volume = "49",

pages = "274 -- 281",

journal = "Nature Genetics",

issn = "1061-4036",

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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

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)).

AB - 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)).

UR - http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3749.html

U2 - 10.1038/ng.3749

DO - 10.1038/ng.3749

M3 - Letter, comment/opinion or interview

C2 - 27992416

SN - 1061-4036

VL - 49

SP - 274

EP - 281

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

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

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