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Journal Articles Molecular Psychiatry Year : 2021

Multi-ancestry genome-wide gene–sleep interactions identify novel loci for blood pressure

Heming Wang (1, 2) , Raymond Noordam , Brian Cade , Karen Schwander , Thomas Winkler , Jiwon Lee (3) , Yun Ju Sung (4) , Amy Bentley , Alisa Manning , Hugues Aschard (5) , Tuomas Kilpeläinen , Marjan Ilkov , Michael Brown , Andrea Horimoto , Melissa Richard , Traci Bartz , Dina Vojinovic , Elise Lim , Jovia Nierenberg , Yongmei Liu , Kumaraswamynaidu Chitrala , Tuomo Rankinen , Solomon Musani , Nora Franceschini , Rainer Rauramaa , Maris Alver , Phyllis Zee , Sarah Harris , Peter van Der Most , Ilja Nolte , Patricia Munroe , Nicholette Palmer , Brigitte Kühnel , Stefan Weiss , Wanqing Wen , Kelly Hall , Leo-Pekka Lyytikäinen , Jeff O'Connell , Gudny Eiriksdottir , Lenore Launer , Paul de Vries , Dan Arking , Han Chen , Eric Boerwinkle , Jose Krieger , Pamela Schreiner , Stephen Sidney , James Shikany , Kenneth Rice , Yii-Der Ida Chen , Sina Gharib , Joshua Bis , Annemarie Luik , M Arfan Ikram , André Uitterlinden , Najaf Amin , Hanfei Xu , Daniel Levy , Jiang He , Kurt Lohman , Alan Zonderman , Treva Rice , Mario Sims , Gregory Wilson , Tamar Sofer , Stephen Rich , Walter Palmas , Jie Yao , Xiuqing Guo , Jerome Rotter , Nienke Biermasz , Dennis Mook-Kanamori , Lisa Martin , Ana Barac , Robert Wallace , Daniel Gottlieb , Pirjo Komulainen , Sami Heikkinen , Reedik Mägi , Lili Milani , Andres Metspalu , John Starr , Yuri Milaneschi , R. Waken , Chuan Gao , Melanie Waldenberger , Annette Peters , Konstantin Strauch , Thomas Meitinger , Till Roenneberg , Uwe Völker , Marcus Dörr , Xiao-Ou Shu , Sutapa Mukherjee , David Hillman , Mika Kähönen , Lynne Wagenknecht , Christian Gieger , Hans Grabe , Wei Zheng , Lyle Palmer , Terho Lehtimäki , Vilmundur Gudnason , Alanna Morrison , Alexandre Pereira , Myriam Fornage , Bruce Psaty , Cornelia van Duijn , Ching-Ti Liu , Tanika Kelly , Michele Evans , Claude Bouchard , Ervin Fox , Charles Kooperberg , Xiaofeng Zhu , Timo Lakka , Tõnu Esko , Kari North , Ian Deary , Harold Snieder , Brenda Penninx , W James Gauderman , Dabeeru Rao , Susan Redline , Diana van Heemst (6)
Raymond Noordam
  • Function : Author
Brian Cade
  • Function : Author
Karen Schwander
  • Function : Author
Thomas Winkler
  • Function : Author
Jiwon Lee
  • Function : Author
Amy Bentley
  • Function : Author
Alisa Manning
  • Function : Author
Tuomas Kilpeläinen
  • Function : Author
Marjan Ilkov
  • Function : Author
Michael Brown
  • Function : Author
Andrea Horimoto
  • Function : Author
Melissa Richard
  • Function : Author
Traci Bartz
  • Function : Author
Dina Vojinovic
  • Function : Author
Elise Lim
  • Function : Author
Jovia Nierenberg
  • Function : Author
Yongmei Liu
  • Function : Author
Kumaraswamynaidu Chitrala
  • Function : Author
Tuomo Rankinen
  • Function : Author
Solomon Musani
  • Function : Author
Nora Franceschini
  • Function : Author
Rainer Rauramaa
  • Function : Author
Maris Alver
  • Function : Author
Phyllis Zee
  • Function : Author
Sarah Harris
Peter van Der Most
  • Function : Author
Ilja Nolte
  • Function : Author
Patricia Munroe
  • Function : Author
Nicholette Palmer
  • Function : Author
Brigitte Kühnel
  • Function : Author
Stefan Weiss
  • Function : Author
Wanqing Wen
  • Function : Author
Kelly Hall
  • Function : Author
Leo-Pekka Lyytikäinen
  • Function : Author
Jeff O'Connell
  • Function : Author
Gudny Eiriksdottir
  • Function : Author
Lenore Launer
  • Function : Author
Paul de Vries
  • Function : Author
Dan Arking
  • Function : Author
Han Chen
Eric Boerwinkle
  • Function : Author
Jose Krieger
  • Function : Author
Pamela Schreiner
  • Function : Author
Stephen Sidney
  • Function : Author
James Shikany
  • Function : Author
Kenneth Rice
  • Function : Author
Yii-Der Ida Chen
  • Function : Author
Sina Gharib
  • Function : Author
Joshua Bis
  • Function : Author
Annemarie Luik
  • Function : Author
M Arfan Ikram
  • Function : Author
André Uitterlinden
  • Function : Author
Najaf Amin
  • Function : Author
Hanfei Xu
  • Function : Author
Daniel Levy
  • Function : Author
Jiang He
  • Function : Author
Kurt Lohman
  • Function : Author
Alan Zonderman
  • Function : Author
Treva Rice
  • Function : Author
Mario Sims
  • Function : Author
Gregory Wilson
  • Function : Author
Tamar Sofer
  • Function : Author
Stephen Rich
  • Function : Author
Walter Palmas
  • Function : Author
Jie Yao
  • Function : Author
Xiuqing Guo
  • Function : Author
Jerome Rotter
  • Function : Author
Nienke Biermasz
  • Function : Author
Dennis Mook-Kanamori
  • Function : Author
Lisa Martin
  • Function : Author
Ana Barac
  • Function : Author
Robert Wallace
  • Function : Author
Daniel Gottlieb
  • Function : Author
Pirjo Komulainen
  • Function : Author
Sami Heikkinen
  • Function : Author
Reedik Mägi
  • Function : Author
Lili Milani
  • Function : Author
Andres Metspalu
  • Function : Author
John Starr
  • Function : Author
Yuri Milaneschi
  • Function : Author
R. Waken
  • Function : Author
Chuan Gao
  • Function : Author
Melanie Waldenberger
  • Function : Author
Annette Peters
Konstantin Strauch
  • Function : Author
Thomas Meitinger
  • Function : Author
Till Roenneberg
  • Function : Author
Uwe Völker
  • Function : Author
Marcus Dörr
  • Function : Author
Xiao-Ou Shu
  • Function : Author
Sutapa Mukherjee
  • Function : Author
David Hillman
  • Function : Author
Mika Kähönen
Lynne Wagenknecht
  • Function : Author
Christian Gieger
  • Function : Author
Hans Grabe
  • Function : Author
Wei Zheng
Lyle Palmer
  • Function : Author
Terho Lehtimäki
  • Function : Author
Vilmundur Gudnason
  • Function : Author
Alanna Morrison
  • Function : Author
Alexandre Pereira
Myriam Fornage
  • Function : Author
Bruce Psaty
  • Function : Author
Cornelia van Duijn
  • Function : Author
Ching-Ti Liu
  • Function : Author
Tanika Kelly
  • Function : Author
Michele Evans
  • Function : Author
Claude Bouchard
  • Function : Author
Ervin Fox
  • Function : Author
Charles Kooperberg
  • Function : Author
Xiaofeng Zhu
  • Function : Author
Timo Lakka
  • Function : Author
Tõnu Esko
  • Function : Author
Kari North
  • Function : Author
Ian Deary
  • Function : Author
Harold Snieder
  • Function : Author
Brenda Penninx
  • Function : Author
W James Gauderman
  • Function : Author
Dabeeru Rao
  • Function : Author
Susan Redline
  • Function : Author

Abstract

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 Pjoint < 5 × 10-8), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (Pint < 5 × 10-8). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (Pint = 2 × 10-6). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (Pint < 10-3). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.

Dates and versions

pasteur-03278749 , version 1 (05-07-2021)

Identifiers

Cite

Heming Wang, Raymond Noordam, Brian Cade, Karen Schwander, Thomas Winkler, et al.. Multi-ancestry genome-wide gene–sleep interactions identify novel loci for blood pressure. Molecular Psychiatry, 2021, 26 (11), pp.6293-6304. ⟨10.1038/s41380-021-01087-0⟩. ⟨pasteur-03278749⟩

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