Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank

Jacqueline M. Lane; Irma Vlasac; Simon G. Anderson; Simon D. Kyle; William G. Dixon; David A. Bechtold; Shubhroz Gill; Max A. Little; Annemarie Luik; Andrew Loudon; Richard Emsley; Frank A.J.L. Scheer; Deborah A. Lawlor; Susan Redline; David W. Ray; Martin K. Rutter; Richa Saxena

doi:10.1038/ncomms10889

Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank

Jacqueline M. Lane, Irma Vlasac, Simon G. Anderson, Simon D. Kyle, William G. Dixon, David A. Bechtold, Shubhroz Gill, Max A. Little, Annemarie Luik, Andrew Loudon, Richard Emsley, Frank A.J.L. Scheer, Deborah A. Lawlor, Susan Redline, David W. Ray, Martin K. Rutter, Richa Saxena^*

^*Corresponding author for this work

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

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Abstract

Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment.

Original language	English
Article number	10889
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms10889
Publication status	Published - 9 Mar 2016
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by NIH grants R21HL121728-02 (R.S.), F32DK102323-01A1 (J.M.L.), R01HL113338-04 (J.M.L., S.R. and R.S.), the University of Manchester (Research Infrastructure Fund), the Wellcome Trust (salary support D.W.R. and A.L.) and UK Medical Research Council MC_UU_12013/5 (D.A.L.). Data on glycemic traits have been contributed by MAGIC investigators and have been downloaded from www.magicinvestigators.org. Data on coronary artery disease/myocardial infarction have been contributed by CARDIo-GRAMplusC4D investigators and have been downloaded from www.CARDIOGRAMPLUSC4D.ORG. We thank the International Genomics of Alzheimer’s Project (IGAP) for providing summary results data for these analyses.

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Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK BiobankFinal published version, 1.33 MBLicence: CC BY

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Lane, J. M., Vlasac, I., Anderson, S. G., Kyle, S. D., Dixon, W. G., Bechtold, D. A., Gill, S., Little, M. A., Luik, A., Loudon, A., Emsley, R., Scheer, F. A. J. L., Lawlor, D. A., Redline, S., Ray, D. W., Rutter, M. K., & Saxena, R. (2016). Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank. Nature Communications, 7, Article 10889. https://doi.org/10.1038/ncomms10889

@article{85d0ae7a0f9545c68c72dc12e406313c,

title = "Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank",

abstract = "Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment.",

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

note = "Funding Information: This work was supported by NIH grants R21HL121728-02 (R.S.), F32DK102323-01A1 (J.M.L.), R01HL113338-04 (J.M.L., S.R. and R.S.), the University of Manchester (Research Infrastructure Fund), the Wellcome Trust (salary support D.W.R. and A.L.) and UK Medical Research Council MC_UU_12013/5 (D.A.L.). Data on glycemic traits have been contributed by MAGIC investigators and have been downloaded from www.magicinvestigators.org. Data on coronary artery disease/myocardial infarction have been contributed by CARDIo-GRAMplusC4D investigators and have been downloaded from www.CARDIOGRAMPLUSC4D.ORG. We thank the International Genomics of Alzheimer{\textquoteright}s Project (IGAP) for providing summary results data for these analyses.",

year = "2016",

month = mar,

day = "9",

doi = "10.1038/ncomms10889",

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journal = "Nature Communications",

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Lane, JM, Vlasac, I, Anderson, SG, Kyle, SD, Dixon, WG, Bechtold, DA, Gill, S, Little, MA, Luik, A, Loudon, A, Emsley, R, Scheer, FAJL, Lawlor, DA, Redline, S, Ray, DW, Rutter, MK & Saxena, R 2016, 'Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank', Nature Communications, vol. 7, 10889. https://doi.org/10.1038/ncomms10889

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T1 - Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank

AU - Lane, Jacqueline M.

AU - Vlasac, Irma

AU - Anderson, Simon G.

AU - Kyle, Simon D.

AU - Dixon, William G.

AU - Bechtold, David A.

AU - Gill, Shubhroz

AU - Little, Max A.

AU - Luik, Annemarie

AU - Loudon, Andrew

AU - Emsley, Richard

AU - Scheer, Frank A.J.L.

AU - Lawlor, Deborah A.

AU - Redline, Susan

AU - Ray, David W.

AU - Rutter, Martin K.

AU - Saxena, Richa

N1 - Funding Information: This work was supported by NIH grants R21HL121728-02 (R.S.), F32DK102323-01A1 (J.M.L.), R01HL113338-04 (J.M.L., S.R. and R.S.), the University of Manchester (Research Infrastructure Fund), the Wellcome Trust (salary support D.W.R. and A.L.) and UK Medical Research Council MC_UU_12013/5 (D.A.L.). Data on glycemic traits have been contributed by MAGIC investigators and have been downloaded from www.magicinvestigators.org. Data on coronary artery disease/myocardial infarction have been contributed by CARDIo-GRAMplusC4D investigators and have been downloaded from www.CARDIOGRAMPLUSC4D.ORG. We thank the International Genomics of Alzheimer’s Project (IGAP) for providing summary results data for these analyses.

PY - 2016/3/9

Y1 - 2016/3/9

N2 - Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment.

AB - Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment.

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DO - 10.1038/ncomms10889

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VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 10889

ER -

Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank

Abstract

Bibliographical note

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