A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations

Pavithra Nagarajan; Thomas W Winkler; Amy R Bentley; Clint L Miller; Aldi T Kraja; Karen Schwander; Songmi Lee; Wenyi Wang; Michael R Brown; John L Morrison; Ayush Giri; Jeffrey R O'Connell; Traci M Bartz; Lisa de Las Fuentes; Valborg Gudmundsdottir; Xiuqing Guo; Sarah E Harris; Zhijie Huang; Mart Kals; Minjung Kho; Christophe Lefevre; Jian'an Luan; Leo-Pekka Lyytikäinen; Massimo Mangino; Yuri Milaneschi; Nicholette D Palmer; Varun Rao; Qian Yang; Jennifer A Smith; Deborah A Lawlor; Million Veteran Program; et al

doi:10.1038/s41380-025-02954-w

A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations

Pavithra Nagarajan, Thomas W Winkler, Amy R Bentley, Clint L Miller, Aldi T Kraja, Karen Schwander, Songmi Lee, Wenyi Wang, Michael R Brown, John L Morrison, Ayush Giri, Jeffrey R O'Connell, Traci M Bartz, Lisa de Las Fuentes, Valborg Gudmundsdottir, Xiuqing Guo, Sarah E Harris, Zhijie Huang, Mart Kals, Minjung KhoChristophe Lefevre, Jian'an Luan, Leo-Pekka Lyytikäinen, Massimo Mangino, Yuri Milaneschi, Nicholette D Palmer, Varun Rao, Qian Yang, Jennifer A Smith, Deborah A Lawlor, Million Veteran Program, et al

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

Abstract

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discovered 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health lifestyle. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausible nature of distinct influences of both sleep duration extremes in cardiovascular health. Several of our loci are specific towards a particular population background or sex, emphasizing the importance of addressing heterogeneity entangled in gene-environment interactions, when considering precision medicine design approaches for blood pressure management.

Original language	English
Pages (from-to)	3660-3672
Number of pages	13
Journal	Molecular Psychiatry
Volume	30
Issue number	8
Early online date	4 Apr 2025
DOIs	https://doi.org/10.1038/s41380-025-02954-w
Publication status	Published - 1 Aug 2025

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature Limited 2025

Keywords

Humans
Blood Pressure/genetics
Sleep/genetics
Genome-Wide Association Study/methods
Male
Female
Middle Aged
Hypertension/genetics
Adult
Polymorphism, Single Nucleotide/genetics
Gene-Environment Interaction
Aged
Genetic Predisposition to Disease/genetics
Sleep Duration

Access to Document

10.1038/s41380-025-02954-w

Handle.net

Persistent link

Cite this

Nagarajan, P., Winkler, T. W., Bentley, A. R., Miller, C. L., Kraja, A. T., Schwander, K., Lee, S., Wang, W., Brown, M. R., Morrison, J. L., Giri, A., O'Connell, J. R., Bartz, T. M., de Las Fuentes, L., Gudmundsdottir, V., Guo, X., Harris, S. E., Huang, Z., Kals, M., ... al , E. (2025). A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations. Molecular Psychiatry, 30(8), 3660-3672. https://doi.org/10.1038/s41380-025-02954-w

@article{93fcb1be4cf64b1c8427acd9e3b8b951,

title = "A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations",

abstract = "Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discovered 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health lifestyle. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausible nature of distinct influences of both sleep duration extremes in cardiovascular health. Several of our loci are specific towards a particular population background or sex, emphasizing the importance of addressing heterogeneity entangled in gene-environment interactions, when considering precision medicine design approaches for blood pressure management.",

keywords = "Humans, Blood Pressure/genetics, Sleep/genetics, Genome-Wide Association Study/methods, Male, Female, Middle Aged, Hypertension/genetics, Adult, Polymorphism, Single Nucleotide/genetics, Gene-Environment Interaction, Aged, Genetic Predisposition to Disease/genetics, Sleep Duration",

author = "Pavithra Nagarajan and Winkler, \{Thomas W\} and Bentley, \{Amy R\} and Miller, \{Clint L\} and Kraja, \{Aldi T\} and Karen Schwander and Songmi Lee and Wenyi Wang and Brown, \{Michael R\} and Morrison, \{John L\} and Ayush Giri and O'Connell, \{Jeffrey R\} and Bartz, \{Traci M\} and \{de Las Fuentes\}, Lisa and Valborg Gudmundsdottir and Xiuqing Guo and Harris, \{Sarah E\} and Zhijie Huang and Mart Kals and Minjung Kho and Christophe Lefevre and Jian'an Luan and Leo-Pekka Lyytik{\"a}inen and Massimo Mangino and Yuri Milaneschi and Palmer, \{Nicholette D\} and Varun Rao and Qian Yang and Smith, \{Jennifer A\} and Lawlor, \{Deborah A\} and \{Million Veteran Program\} and et al",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature Limited 2025",

year = "2025",

month = aug,

day = "1",

doi = "10.1038/s41380-025-02954-w",

language = "English",

volume = "30",

pages = "3660--3672",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Springer Nature",

number = "8",

}

Nagarajan, P, Winkler, TW, Bentley, AR, Miller, CL, Kraja, AT, Schwander, K, Lee, S, Wang, W, Brown, MR, Morrison, JL, Giri, A, O'Connell, JR, Bartz, TM, de Las Fuentes, L, Gudmundsdottir, V, Guo, X, Harris, SE, Huang, Z, Kals, M, Kho, M, Lefevre, C, Luan, J, Lyytikäinen, L-P, Mangino, M, Milaneschi, Y, Palmer, ND, Rao, V, Yang, Q, Smith, JA, Lawlor, DA, Million Veteran Program & al , E 2025, 'A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations', Molecular Psychiatry, vol. 30, no. 8, pp. 3660-3672. https://doi.org/10.1038/s41380-025-02954-w

TY - JOUR

T1 - A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations

AU - Nagarajan, Pavithra

AU - Winkler, Thomas W

AU - Bentley, Amy R

AU - Miller, Clint L

AU - Kraja, Aldi T

AU - Schwander, Karen

AU - Lee, Songmi

AU - Wang, Wenyi

AU - Brown, Michael R

AU - Morrison, John L

AU - Giri, Ayush

AU - O'Connell, Jeffrey R

AU - Bartz, Traci M

AU - de Las Fuentes, Lisa

AU - Gudmundsdottir, Valborg

AU - Guo, Xiuqing

AU - Harris, Sarah E

AU - Huang, Zhijie

AU - Kals, Mart

AU - Kho, Minjung

AU - Lefevre, Christophe

AU - Luan, Jian'an

AU - Lyytikäinen, Leo-Pekka

AU - Mangino, Massimo

AU - Milaneschi, Yuri

AU - Palmer, Nicholette D

AU - Rao, Varun

AU - Yang, Qian

AU - Smith, Jennifer A

AU - Lawlor, Deborah A

AU - Million Veteran Program

AU - al , et

PY - 2025/8/1

Y1 - 2025/8/1

N2 - Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discovered 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health lifestyle. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausible nature of distinct influences of both sleep duration extremes in cardiovascular health. Several of our loci are specific towards a particular population background or sex, emphasizing the importance of addressing heterogeneity entangled in gene-environment interactions, when considering precision medicine design approaches for blood pressure management.

AB - Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discovered 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health lifestyle. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausible nature of distinct influences of both sleep duration extremes in cardiovascular health. Several of our loci are specific towards a particular population background or sex, emphasizing the importance of addressing heterogeneity entangled in gene-environment interactions, when considering precision medicine design approaches for blood pressure management.

KW - Humans

KW - Blood Pressure/genetics

KW - Sleep/genetics

KW - Genome-Wide Association Study/methods

KW - Male

KW - Female

KW - Middle Aged

KW - Hypertension/genetics

KW - Adult

KW - Polymorphism, Single Nucleotide/genetics

KW - Gene-Environment Interaction

KW - Aged

KW - Genetic Predisposition to Disease/genetics

KW - Sleep Duration

U2 - 10.1038/s41380-025-02954-w

DO - 10.1038/s41380-025-02954-w

M3 - Article (Academic Journal)

C2 - 40181193

SN - 1359-4184

VL - 30

SP - 3660

EP - 3672

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 8

ER -

A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations

Abstract

Bibliographical note

Keywords

Access to Document

Handle.net

Fingerprint

Cite this