A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations

Author:

Wang Heming1ORCID,Nagarajan Pavithra,Winkler Thomas,Bentley Amy2ORCID,Miller Clint,Kraja Aldi,Schwander Karen,Lee Songmi,Wang Wenyi,Brown Michael3ORCID,Morrison John,Giri Ayush,O'Connell Jeffrey,Bartz Traci,Fuentes Lisa de las4ORCID,Gudmundsdottir Valborg,Guo Xiuqing5ORCID,Harris Sarah6ORCID,Huang Zhijie,Kals Mart,Kho Minjung,Lefevre ChristopheORCID,Luan Jian'an7ORCID,Lyytikäinen Leo-Pekka8ORCID,Mangino Massimo9ORCID,Milaneschi Y10,Palmer Nicholette11ORCID,Rao Varun,Rauramaa Rainer,Shen Botong,Stadler Stefan,Sun Quan12ORCID,Tang Jingxian,Thériault Sébastien,Graaf Adriaan van der,Most Peter van derORCID,Wang Yujie,Weiss Stefan13ORCID,Westerman Kenneth,Yang Qian,Yasuharu Tabara,Zhao Wei14ORCID,Zhu Wanying,Altschul Drew,Ansari Md Abu Yusuf,Anugu Pramod,Argoty-Pantoja Anna,Arzt Michael,Aschard Hugues15,Attia JohnORCID,Bazzano Lydia16,Breyer Max,Brody Jennifer,Cade Brian1ORCID,Chen Hung-hsin17ORCID,Chen Yii-Der Ida,Chen Zekai,de Vries Paul18ORCID,Dimitrov Latchezar,Do Ahn,Du JiawenORCID,Dupont CharlesORCID,Edwards Todd,Evans Michele19,Faquih Tariq,Felix Stephan,Fisher-Hoch Susan,Floyd James,Graff Mariaelisa20ORCID,Gu C. Charles21ORCID,Gu Dongfeng,Hairston Kristen,Hanley Anthony,Heid Iris22ORCID,Heikkinen Sami23ORCID,Highland Heather24ORCID,Hood Michelle,Kähönen Mika25,Karvonen-Gutierrez Carrie,Kawaguchi Takahisa,Kazuya Setoh,Tanika Kelly26,Komulainen Pirjo,Levy Daniel,Lin Henry,Liu PeterORCID,Marques-Vidal Pedro,McCormick Joseph27ORCID,Mei Hao28,Meigs James,Menni Cristina9ORCID,Nam Kisung29ORCID,Nolte Ilja30ORCID,Pacheco Natasha,Petty Lauren,Polikowsky Hannah,Province Michael21ORCID,Psaty Bruce31ORCID,Raffield Laura,Raitakari Olli32,Rich Stephen33ORCID,Riha Renata,Risch Lorenz,Risch Martin,Ruiz-Narvaez Edward,Scott Rodney34ORCID,Sitlani Colleen,Smith Jennifer14ORCID,Sofer Tamar35ORCID,Teder-Laving Maris,Völker Uwe36ORCID,Vollenweider Peter37,Wang Guanchao,Dijk Ko WIllems van38ORCID,Wilson Otis,Xia Rui39,Yao Jie,Young Kristin,Zhang Ruiyuan,Zhu Xiaofeng40ORCID,Below Jennifer17ORCID,Böger Carsten,Conen David,Cox Simon41ORCID,Dörr Marcus36ORCID,Feitosa Mary4ORCID,Fox Ervin,Franceschini Nora,Gharib Sina42ORCID,Gudnason Vilmundur43ORCID,Harlow Sioban,He Jiang44,Holliday Elizabeth45,Kutalik Zoltan,Lakka Timo,Lawlor Deborah46ORCID,Lee Seunggeun,Lehtimäki Terho47ORCID,Li Changwei48ORCID,Liu Ching-Ti49ORCID,Mägi Reedik,Matsuda Fumihiko,Morrison Alanna3ORCID,Penninx Brenda W.J.H.,Peyser Patricia50ORCID,Rotter Jerome51ORCID,Snieder Harold52ORCID,Spector T,Wagenknecht Lynne,Wareham Nicholas7ORCID,Zonderman Alan53ORCID,North Kari54ORCID,Fornage Myriam55ORCID,Hung Adriana,Manning Alisa,Gauderman W.,Chen Han,Munroe Patricia,Rao Dabeeru56,Heemst Diana van,Redline Susan1ORCID,Noordam Raymond38

Affiliation:

1. Brigham and Women's Hospital

2. National Institutes of Health, NHGRI

3. The University of Texas Health Science Center at Houston

4. Washington University School of Medicine

5. The Lundquist Institute

6. The University of Edinburgh

7. University of Cambridge

8. Fimlab Laboratories and Finnish Cardiovascular Research Center

9. King's College London

10. VU University Medical Center

11. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai

12. University of North Carolina, USA

13. University Medicine Greifswald & University of Greifswald

14. University of Michigan

15. Institut Pasteur

16. Louisiana State University

17. Vanderbilt University Medical Center

18. Human Genetics Center

19. National Institute on Aging

20. University of North Carolina

21. Washington University

22. University of Regensburg

23. Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus

24. University of North Carolina at Chapel Hill

25. Tampere University

26. University of Illinois Chicago

27. The University of Texas Health Science Center at Houston (UTHealth) School of Public Health

28. University of Mississippi Medical Center

29. Seoul National University

30. University of Groningen, University Medical Center Groningen

31. Cardiovascular Health Research Unit

32. Turku University Hospital and Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku

33. University of Virginia

34. University of Newcastle and the Hunter Medical Research Institute

35. Harvard University

36. University Medicine Greifswald

37. Lausanne University Hospital (CHUV)

38. Leiden University Medical Center

39. The Brown Foundation Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston

40. Case Western Reserve University

41. University of Edinburgh

42. University of Washington

43. Icelandic Heart Association

44. Tulane University School of Public Health and Tropical Medicine

45. Hunter Medical Research Institute

46. University of Bristol

47. Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University

48. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA

49. Boston University School of Public Health

50. Department of Epidemiology, School of Public Health, University of Michigan

51. The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

52. University Medical Center Groningen

53. National Institute on Aging, NIA/NIH/IRP

54. UNC Chapel Hill

55. 1. Institute of Molecular Medicine, McGovern Medical School, The University of Texas Health Science Center 2. Human Genetics Center, Department of Epidemiology, School of Public Health

56. Washington University in St. Louis

Abstract

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 discover 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.

Publisher

Springer Science and Business Media LLC

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