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

Million Veteran Program; 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; 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

Million Veteran Program, 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, John Concato, Daniel J. Buysse, J. Michael Gaziano, Daniel J. Gottlieb, Renato Polimanti, Murray B. Stein, Elvira Bramon, Joel Gelernter^*

^*Corresponding author for this work

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

10 Citations (Scopus)

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 (rg = 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.

Original language	English
Pages (from-to)	6059
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-41249-y
Publication status	Published - 28 Sept 2023

Keywords

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

Access to Document

10.1038/s41467-023-41249-yLicence: CC BY

Cite this

Million Veteran Program, Austin-Zimmerman, I., Levey, D. F., Giannakopoulou, O., Deak, J. D., Galimberti, M., Adhikari, K., Zhou, H., Denaxas, S., Irizar, H., Kuchenbaecker, K., McQuillin, A., Concato, J., Buysse, D. J., Gaziano, J. M., Gottlieb, D. J., Polimanti, R., Stein, M. B., Bramon, E., & Gelernter, J. (2023). Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration. Nature Communications, 14(1), 6059. https://doi.org/10.1038/s41467-023-41249-y

@article{a192c4b45a31493e91da184c79896ab1,

title = "Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration",

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 (rg = 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.",

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

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

note = "{\textcopyright} 2023. Springer Nature Limited.",

year = "2023",

month = sep,

day = "28",

doi = "10.1038/s41467-023-41249-y",

language = "English",

volume = "14",

pages = "6059",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Million Veteran Program, Austin-Zimmerman, I, Levey, DF, Giannakopoulou, O, Deak, JD, Galimberti, M, Adhikari, K, Zhou, H, Denaxas, S, Irizar, H, Kuchenbaecker, K, McQuillin, A, Concato, J, Buysse, DJ, Gaziano, JM, Gottlieb, DJ, Polimanti, R, Stein, MB, Bramon, E & Gelernter, J 2023, 'Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration', Nature Communications, vol. 14, no. 1, pp. 6059. https://doi.org/10.1038/s41467-023-41249-y

TY - JOUR

T1 - Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration

AU - Million Veteran Program

AU - Austin-Zimmerman, Isabelle

AU - Levey, Daniel F.

AU - Giannakopoulou, Olga

AU - Deak, Joseph D.

AU - Galimberti, Marco

AU - Adhikari, Keyrun

AU - Zhou, Hang

AU - Denaxas, Spiros

AU - Irizar, Haritz

AU - Kuchenbaecker, Karoline

AU - McQuillin, Andrew

AU - Concato, John

AU - Buysse, Daniel J.

AU - Gaziano, J. Michael

AU - Gottlieb, Daniel J.

AU - Polimanti, Renato

AU - Stein, Murray B.

AU - Bramon, Elvira

AU - Gelernter, Joel

PY - 2023/9/28

Y1 - 2023/9/28

N2 - 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 (rg = 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.

AB - 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 (rg = 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.

KW - Adult

KW - Humans

KW - Sleep Duration

KW - Genome-Wide Association Study

KW - Polymorphism, Single Nucleotide

KW - Sleep/genetics

KW - Phenotype

KW - Mendelian Randomization Analysis

U2 - 10.1038/s41467-023-41249-y

DO - 10.1038/s41467-023-41249-y

M3 - Article

C2 - 37770476

SN - 2041-1723

VL - 14

SP - 6059

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this