Genome-wide association analysis of composite sleep health scores in 413,904 individuals

Matthew O. Goodman; Tariq Faquih; Valentina Paz; Pavithra Nagarajan; Jacqueline M. Lane; Brian Spitzer; Matthew Maher; Joon Chung; Brian E. Cade; Shaun M. Purcell; Xiaofeng Zhu; Raymond Noordam; Andrew J. K. Phillips; Simon D. Kyle; Kai Spiegelhalder; Michael N. Weedon; Deborah A. Lawlor; Jerome I. Rotter; Kent D. Taylor; Carmen R. Isasi; Tamar Sofer; Hassan S. Dashti; Martin K. Rutter; Susan Redline; Richa Saxena; Heming Wang

doi:10.1038/s42003-025-07514-0

Genome-wide association analysis of composite sleep health scores in 413,904 individuals

Matthew O. Goodman, Tariq Faquih, Valentina Paz, Pavithra Nagarajan, Jacqueline M. Lane, Brian Spitzer, Matthew Maher, Joon Chung, Brian E. Cade, Shaun M. Purcell, Xiaofeng Zhu, Raymond Noordam, Andrew J. K. Phillips, Simon D. Kyle, Kai Spiegelhalder, Michael N. Weedon, Deborah A. Lawlor, Jerome I. Rotter, Kent D. Taylor, Carmen R. IsasiTamar Sofer, Hassan S. Dashti, Martin K. Rutter, Susan Redline, Richa Saxena, Heming Wang^*

^*Corresponding author for this work

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

1 Citation (Scopus)

Abstract

Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, so together may provide a more complete picture of sleep health, while illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p < 8.3e-9), along with 341 previously reported loci (p < 5e-08). The heritability of the first three SHS-PCs equals or exceeds that of SHS-ADD (SNP-h2 = 0.094), while revealing sleep-domain-specific genetic discoveries. Significant loci enrich in multiple brain tissues and in metabolic and neuronal pathways. Post-GWAS analyses uncover novel genetic mechanisms underlying sleep health and reveal connections (including potential causal links) to behavioral, psychological, and cardiometabolic traits.

Original language	English
Article number	115
Number of pages	15
Journal	Communications Biology
Volume	8
Issue number	1
Early online date	24 Jan 2025
DOIs	https://doi.org/10.1038/s42003-025-07514-0
Publication status	E-pub ahead of print - 24 Jan 2025

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© 2025. The Author(s).

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Goodman, M. O., Faquih, T., Paz, V., Nagarajan, P., Lane, J. M., Spitzer, B., Maher, M., Chung, J., Cade, B. E., Purcell, S. M., Zhu, X., Noordam, R., Phillips, A. J. K., Kyle, S. D., Spiegelhalder, K., Weedon, M. N., Lawlor, D. A., Rotter, J. I., Taylor, K. D., ... Wang, H. (2025). Genome-wide association analysis of composite sleep health scores in 413,904 individuals. Communications Biology, 8(1), Article 115. Advance online publication. https://doi.org/10.1038/s42003-025-07514-0

@article{6f0abefb71a54d08bd55a96b29141310,

title = "Genome-wide association analysis of composite sleep health scores in 413,904 individuals",

abstract = "Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, so together may provide a more complete picture of sleep health, while illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p < 8.3e-9), along with 341 previously reported loci (p < 5e-08). The heritability of the first three SHS-PCs equals or exceeds that of SHS-ADD (SNP-h2 = 0.094), while revealing sleep-domain-specific genetic discoveries. Significant loci enrich in multiple brain tissues and in metabolic and neuronal pathways. Post-GWAS analyses uncover novel genetic mechanisms underlying sleep health and reveal connections (including potential causal links) to behavioral, psychological, and cardiometabolic traits.",

author = "Goodman, \{Matthew O.\} and Tariq Faquih and Valentina Paz and Pavithra Nagarajan and Lane, \{Jacqueline M.\} and Brian Spitzer and Matthew Maher and Joon Chung and Cade, \{Brian E.\} and Purcell, \{Shaun M.\} and Xiaofeng Zhu and Raymond Noordam and Phillips, \{Andrew J. K.\} and Kyle, \{Simon D.\} and Kai Spiegelhalder and Weedon, \{Michael N.\} and Lawlor, \{Deborah A.\} and Rotter, \{Jerome I.\} and Taylor, \{Kent D.\} and Isasi, \{Carmen R.\} and Tamar Sofer and Dashti, \{Hassan S.\} and Rutter, \{Martin K.\} and Susan Redline and Richa Saxena and Heming Wang",

note = "Publisher Copyright: {\textcopyright} 2025. The Author(s).",

year = "2025",

month = jan,

day = "24",

doi = "10.1038/s42003-025-07514-0",

language = "English",

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Goodman, MO, Faquih, T, Paz, V, Nagarajan, P, Lane, JM, Spitzer, B, Maher, M, Chung, J, Cade, BE, Purcell, SM, Zhu, X, Noordam, R, Phillips, AJK, Kyle, SD, Spiegelhalder, K, Weedon, MN, Lawlor, DA, Rotter, JI, Taylor, KD, Isasi, CR, Sofer, T, Dashti, HS, Rutter, MK, Redline, S, Saxena, R & Wang, H 2025, 'Genome-wide association analysis of composite sleep health scores in 413,904 individuals', Communications Biology, vol. 8, no. 1, 115. https://doi.org/10.1038/s42003-025-07514-0

TY - JOUR

T1 - Genome-wide association analysis of composite sleep health scores in 413,904 individuals

AU - Goodman, Matthew O.

AU - Faquih, Tariq

AU - Paz, Valentina

AU - Nagarajan, Pavithra

AU - Lane, Jacqueline M.

AU - Spitzer, Brian

AU - Maher, Matthew

AU - Chung, Joon

AU - Cade, Brian E.

AU - Purcell, Shaun M.

AU - Zhu, Xiaofeng

AU - Noordam, Raymond

AU - Phillips, Andrew J. K.

AU - Kyle, Simon D.

AU - Spiegelhalder, Kai

AU - Weedon, Michael N.

AU - Lawlor, Deborah A.

AU - Rotter, Jerome I.

AU - Taylor, Kent D.

AU - Isasi, Carmen R.

AU - Sofer, Tamar

AU - Dashti, Hassan S.

AU - Rutter, Martin K.

AU - Redline, Susan

AU - Saxena, Richa

AU - Wang, Heming

PY - 2025/1/24

Y1 - 2025/1/24

N2 - Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, so together may provide a more complete picture of sleep health, while illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p < 8.3e-9), along with 341 previously reported loci (p < 5e-08). The heritability of the first three SHS-PCs equals or exceeds that of SHS-ADD (SNP-h2 = 0.094), while revealing sleep-domain-specific genetic discoveries. Significant loci enrich in multiple brain tissues and in metabolic and neuronal pathways. Post-GWAS analyses uncover novel genetic mechanisms underlying sleep health and reveal connections (including potential causal links) to behavioral, psychological, and cardiometabolic traits.

AB - Recent genome-wide association studies (GWASs) of several individual sleep traits have identified hundreds of genetic loci, suggesting diverse mechanisms. Moreover, sleep traits are moderately correlated, so together may provide a more complete picture of sleep health, while illuminating distinct domains. Here we construct novel sleep health scores (SHSs) incorporating five core self-report measures: sleep duration, insomnia symptoms, chronotype, snoring, and daytime sleepiness, using additive (SHS-ADD) and five principal components-based (SHS-PCs) approaches. GWASs of these six SHSs identify 28 significant novel loci adjusting for multiple testing on six traits (p < 8.3e-9), along with 341 previously reported loci (p < 5e-08). The heritability of the first three SHS-PCs equals or exceeds that of SHS-ADD (SNP-h2 = 0.094), while revealing sleep-domain-specific genetic discoveries. Significant loci enrich in multiple brain tissues and in metabolic and neuronal pathways. Post-GWAS analyses uncover novel genetic mechanisms underlying sleep health and reveal connections (including potential causal links) to behavioral, psychological, and cardiometabolic traits.

U2 - 10.1038/s42003-025-07514-0

DO - 10.1038/s42003-025-07514-0

M3 - Article (Academic Journal)

C2 - 39856408

SN - 2399-3642

VL - 8

JO - Communications Biology

JF - Communications Biology

IS - 1

M1 - 115

ER -

Genome-wide association analysis of composite sleep health scores in 413,904 individuals

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