Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms

Samuel E. Jones; Jacqueline M. Lane; Andrew R. Wood; Vincent T. van Hees; Jessica Tyrrell; Robin N. Beaumont; Aaron R. Jeffries; Hassan S. Dashti; Melvyn Hillsdon; Katherine S. Ruth; Marcus A. Tuke; Hanieh Yaghootkar; Seth A. Sharp; Yingjie Jie; William D. Thompson; Jamie W. Harrison; Amy Dawes; Enda M. Byrne; Henning Tiemeier; Karla V. Allebrandt; Jack Bowden; David W. Ray; Rachel M. Freathy; Anna Murray; Diego R. Mazzotti; Philip R. Gehrman; Debbie A. Lawlor; Timothy M. Frayling; Martin K. Rutter; David A. Hinds; Richa Saxena; Michael N. Weedon

doi:10.1038/s41467-018-08259-7

Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms

Samuel E. Jones, Jacqueline M. Lane, Andrew R. Wood, Vincent T. van Hees, Jessica Tyrrell, Robin N. Beaumont, Aaron R. Jeffries, Hassan S. Dashti, Melvyn Hillsdon, Katherine S. Ruth, Marcus A. Tuke, Hanieh Yaghootkar, Seth A. Sharp, Yingjie Jie, William D. Thompson, Jamie W. Harrison, Amy Dawes, Enda M. Byrne, Henning Tiemeier, Karla V. AllebrandtJack Bowden, David W. Ray, Rachel M. Freathy, Anna Murray, Diego R. Mazzotti, Philip R. Gehrman, Debbie A. Lawlor, Timothy M. Frayling, Martin K. Rutter, David A. Hinds, Richa Saxena, Michael N. Weedon^*

^*Corresponding author for this work

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Abstract

Being a morning person is a behavioural indicator of a person’s underlying circadian rhythm. Using genome-wide data from 697,828 UK Biobank and 23andMe participants we increase the number of genetic loci associated with being a morning person from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we find that the chronotype loci associate with sleep timing: the mean sleep timing of the 5% of individuals carrying the most morningness alleles is 25 min earlier than the 5% carrying the fewest. The loci are enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. Using Mendelian Randomisation, we show that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes. This study offers insights into circadian biology and its links to disease in humans.

Original language	English
Article number	343
Number of pages	11
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-08259-7
Publication status	Published - 29 Jan 2019

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Jones, S. E., Lane, J. M., Wood, A. R., van Hees, V. T., Tyrrell, J., Beaumont, R. N., Jeffries, A. R., Dashti, H. S., Hillsdon, M., Ruth, K. S., Tuke, M. A., Yaghootkar, H., Sharp, S. A., Jie, Y., Thompson, W. D., Harrison, J. W., Dawes, A., Byrne, E. M., Tiemeier, H., ... Weedon, M. N. (2019). Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms. Nature Communications, 10(1), Article 343. https://doi.org/10.1038/s41467-018-08259-7

@article{2e80f86cd4c14427824d5b8ff0d961cd,

title = "Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms",

abstract = "Being a morning person is a behavioural indicator of a person{\textquoteright}s underlying circadian rhythm. Using genome-wide data from 697,828 UK Biobank and 23andMe participants we increase the number of genetic loci associated with being a morning person from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we find that the chronotype loci associate with sleep timing: the mean sleep timing of the 5% of individuals carrying the most morningness alleles is 25 min earlier than the 5% carrying the fewest. The loci are enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. Using Mendelian Randomisation, we show that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes. This study offers insights into circadian biology and its links to disease in humans.",

author = "Jones, {Samuel E.} and Lane, {Jacqueline M.} and Wood, {Andrew R.} and {van Hees}, {Vincent T.} and Jessica Tyrrell and Beaumont, {Robin N.} and Jeffries, {Aaron R.} and Dashti, {Hassan S.} and Melvyn Hillsdon and Ruth, {Katherine S.} and Tuke, {Marcus A.} and Hanieh Yaghootkar and Sharp, {Seth A.} and Yingjie Jie and Thompson, {William D.} and Harrison, {Jamie W.} and Amy Dawes and Byrne, {Enda M.} and Henning Tiemeier and Allebrandt, {Karla V.} and Jack Bowden and Ray, {David W.} and Freathy, {Rachel M.} and Anna Murray and Mazzotti, {Diego R.} and Gehrman, {Philip R.} and Lawlor, {Debbie A.} and Frayling, {Timothy M.} and Rutter, {Martin K.} and Hinds, {David A.} and Richa Saxena and Weedon, {Michael N.}",

year = "2019",

month = jan,

day = "29",

doi = "10.1038/s41467-018-08259-7",

language = "English",

volume = "10",

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issn = "2041-1723",

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Jones, SE, Lane, JM, Wood, AR, van Hees, VT, Tyrrell, J, Beaumont, RN, Jeffries, AR, Dashti, HS, Hillsdon, M, Ruth, KS, Tuke, MA, Yaghootkar, H, Sharp, SA, Jie, Y, Thompson, WD, Harrison, JW, Dawes, A, Byrne, EM, Tiemeier, H, Allebrandt, KV, Bowden, J, Ray, DW, Freathy, RM, Murray, A, Mazzotti, DR, Gehrman, PR, Lawlor, DA, Frayling, TM, Rutter, MK, Hinds, DA, Saxena, R & Weedon, MN 2019, 'Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms', Nature Communications, vol. 10, no. 1, 343. https://doi.org/10.1038/s41467-018-08259-7

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T1 - Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms

AU - Jones, Samuel E.

AU - Lane, Jacqueline M.

AU - Wood, Andrew R.

AU - van Hees, Vincent T.

AU - Tyrrell, Jessica

AU - Beaumont, Robin N.

AU - Jeffries, Aaron R.

AU - Dashti, Hassan S.

AU - Hillsdon, Melvyn

AU - Ruth, Katherine S.

AU - Tuke, Marcus A.

AU - Yaghootkar, Hanieh

AU - Sharp, Seth A.

AU - Jie, Yingjie

AU - Thompson, William D.

AU - Harrison, Jamie W.

AU - Dawes, Amy

AU - Byrne, Enda M.

AU - Tiemeier, Henning

AU - Allebrandt, Karla V.

AU - Bowden, Jack

AU - Ray, David W.

AU - Freathy, Rachel M.

AU - Murray, Anna

AU - Mazzotti, Diego R.

AU - Gehrman, Philip R.

AU - Lawlor, Debbie A.

AU - Frayling, Timothy M.

AU - Rutter, Martin K.

AU - Hinds, David A.

AU - Saxena, Richa

AU - Weedon, Michael N.

PY - 2019/1/29

Y1 - 2019/1/29

N2 - Being a morning person is a behavioural indicator of a person’s underlying circadian rhythm. Using genome-wide data from 697,828 UK Biobank and 23andMe participants we increase the number of genetic loci associated with being a morning person from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we find that the chronotype loci associate with sleep timing: the mean sleep timing of the 5% of individuals carrying the most morningness alleles is 25 min earlier than the 5% carrying the fewest. The loci are enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. Using Mendelian Randomisation, we show that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes. This study offers insights into circadian biology and its links to disease in humans.

AB - Being a morning person is a behavioural indicator of a person’s underlying circadian rhythm. Using genome-wide data from 697,828 UK Biobank and 23andMe participants we increase the number of genetic loci associated with being a morning person from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we find that the chronotype loci associate with sleep timing: the mean sleep timing of the 5% of individuals carrying the most morningness alleles is 25 min earlier than the 5% carrying the fewest. The loci are enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. Using Mendelian Randomisation, we show that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes. This study offers insights into circadian biology and its links to disease in humans.

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UR - https://www.biorxiv.org/content/10.1101/303941v2

U2 - 10.1038/s41467-018-08259-7

DO - 10.1038/s41467-018-08259-7

M3 - Article (Academic Journal)

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AN - SCOPUS:85060800167

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 343

ER -

Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms

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Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms

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