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

Commun Biol. 2025 Jan 24;8(1):115. doi: 10.1038/s42003-025-07514-0.

Authors

Matthew O Goodman^{1

2

3}, Tariq Faquih^{1

2

3}, Valentina Paz^{4

5

6}, Pavithra Nagarajan¹, Jacqueline M Lane^{1

2

3

6}, Brian Spitzer⁷, Matthew Maher⁶, Joon Chung⁸, Brian E Cade^{1

2

3}, Shaun M Purcell^{1

2

3

9}, Xiaofeng Zhu¹⁰, Raymond Noordam¹¹, Andrew J K Phillips¹², Simon D Kyle¹³, Kai Spiegelhalder¹⁴, Michael N Weedon¹⁵, Deborah A Lawlor^{16

17}, Jerome I Rotter¹⁸, Kent D Taylor¹⁸, Carmen R Isasi¹⁹, Tamar Sofer^{1

2

7

20}, Hassan S Dashti^{3

6

21}, Martin K Rutter^{22

23}, Susan Redline^{1

2}, Richa Saxena^{3

6

21}, Heming Wang^{24

25}

Affiliations

¹ Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.
² Department of Neurology and Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
³ Broad Institute, Cambridge, MA, USA.
⁴ Instituto de Psicología Clínica, Facultad de Psicología, Universidad de la República, Montevideo, Uruguay.
⁵ MRC Unit for Lifelong Health & Ageing, Institute of Cardiovascular Science, University College London, London, United Kingdom.
⁶ Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁸ Department of Informatics and Health Data Science, Miller School of Medicine, University of Miami, Miami, FL, USA.
⁹ Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA.
¹⁰ Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
¹¹ Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
¹² School of Psychological Sciences, Turner Institute for Brain and Mental Health, Monash University, Melbourne, VIC, Australia.
¹³ Sir Jules Thorn Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
¹⁴ Department of Psychiatry and Psychotherapy, Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
¹⁵ Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK.
¹⁶ MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
¹⁷ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
¹⁸ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
¹⁹ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
²⁰ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
²¹ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
²² Division of Endocrinology, Diabetes & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
²³ Diabetes, Endocrinology and Metabolism Centre, Manchester University NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester, UK.
²⁴ Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA. [email protected].
²⁵ Department of Neurology and Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA. [email protected].

PMID: 39856408
DOI: 10.1038/s42003-025-07514-0

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.

MeSH terms

Adult
Female
Genome-Wide Association Study*
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Sleep* / genetics

Abstract

MeSH terms

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