Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration

Isabelle Austin-Zimmerman; Daniel F Levey; Olga Giannakopoulou; Joseph D Deak; Marco Galimberti; Keyrun Adhikari; Hang Zhou; Spiros Denaxas; Haritz Irizar; Karoline Kuchenbaecker; Andrew McQuillin; Million Veteran Program; John Concato; Daniel J Buysse; J Michael Gaziano; Daniel J Gottlieb; Renato Polimanti; Murray B Stein; Elvira Bramon; Joel Gelernter

doi:10.1038/s41467-023-41249-y

Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration

Nat Commun. 2023 Sep 28;14(1):6059. doi: 10.1038/s41467-023-41249-y.

Authors

Isabelle Austin-Zimmerman^{1

2}, Daniel F Levey^{3

4}, Olga Giannakopoulou^{1

5}, Joseph D Deak^{3

4}, Marco Galimberti^{3

4}, Keyrun Adhikari^{3

4}, Hang Zhou^{3

4}, Spiros Denaxas⁶, Haritz Irizar^{1

7}, Karoline Kuchenbaecker^{1

5}, Andrew McQuillin¹; Million Veteran Program; John Concato^{8

9}, Daniel J Buysse¹⁰, J Michael Gaziano^{11

12}, Daniel J Gottlieb^{13

14

15}, Renato Polimanti^{3

4}, Murray B Stein^{16

17}, Elvira Bramon^{1

18}, Joel Gelernter^{19

20}

Affiliations

¹ Department of Mental Health Neuroscience, Division of Psychiatry, University College London, London, W1T 7BN, UK.
² Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.
³ Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
⁴ Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.
⁵ UCL Genetics Institute, Division of Biosciences, University College London, London, WC1E 6BT, UK.
⁶ Health Data Research UK, Institute of Health Informatics, University College London, London, NW1 2DA, UK.
⁷ Department of Genetics & Genomic Sciences and Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁸ School of Medicine, Yale University, New Haven, CT, 06511, USA.
⁹ Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration (FDA), Silver Spring, MD, USA.
¹⁰ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
¹¹ Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, 02130, USA.
¹² Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
¹³ VA Boston Healthcare System, 1400 VFW Parkway (111PI), West Roxbury, MA, 02132, USA.
¹⁴ Division of Sleep and Circadian Disorders, Brigham & Women's Hospital, Boston, MA, USA.
¹⁵ Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
¹⁶ Psychiatry Service, VA San Diego Healthcare System, San Diego, CA, USA.
¹⁷ Departments of Psychiatry and Herbert Wertheim School of Public Health, University of California, San Diego, La Jolla, CA, USA.
¹⁸ Institute of Cognitive Neuroscience, University College London, London, UK.
¹⁹ Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. joel.gelernter@yale.edu.
²⁰ Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA. joel.gelernter@yale.edu.

Abstract

Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (r_g = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.

Trial registration: ClinicalTrials.gov NCT02256644.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Genome-Wide Association Study*
Humans
Mendelian Randomization Analysis
Phenotype
Polymorphism, Single Nucleotide
Sleep / genetics
Sleep Duration*

Associated data

ClinicalTrials.gov/NCT02256644

Abstract

Publication types

MeSH terms

Associated data

Grants and funding