Rxivist logo

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

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

Posted 31 May 2020
bioRxiv DOI: 10.1101/2020.05.29.123505

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 using 1 degree of freedom (1df) interaction and 2df joint tests. Primary multi-ancestry analyses in 62,969 individuals in stage 1 identified 3 novel loci that were replicated in an additional 59,296 individuals in stage 2, including rs7955964 (FIGNL2/ANKRD33) showing significant 1df interactions with long sleep duration and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) showing significant 1df interactions with short sleep duration. Secondary ancestry-specific two-stage analyses and combined stage 1 and 2 analyses additionally identified 23 novel loci that need external replication, including 3 and 5 loci showing significant 1df interactions with long and short sleep duration, respectively. Multiple genes mapped to our 26 novel loci have known functions in sleep-wake regulation, nervous and cardiometabolic systems. We also identified new gene by long sleep interactions near five known BP loci (≤1Mb) including NME7, FAM208A, MKLN1, CEP164, and RGL3/ELAVL3. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation. ### Competing Interest Statement D.O.M.K. is a part time research consultant at Metabolon, Inc. B.M.P. serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. H.J.G. has received research support from the German Research Foundation (DFG), the German Ministry of Education and Research (BMBF), the DAMP Foundation, Fresenius Medical Care, the EU Joint Programme Neurodegenerative Disorders (JPND) and the European Social Fund (ESF). The remaining authors declare no competing interests.

Download data

  • Downloaded 164 times
  • Download rankings, all-time:
    • Site-wide: 84,927 out of 101,039
    • In genomics: 5,713 out of 6,265
  • Year to date:
    • Site-wide: 37,556 out of 101,039
  • Since beginning of last month:
    • Site-wide: 37,715 out of 101,039

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


  • 20 Oct 2020: Support for sorting preprints using Twitter activity has been removed, at least temporarily, until a new source of social media activity data becomes available.
  • 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
  • 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
  • 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
  • 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
  • 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
  • 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
  • 22 Jan 2019: Nature just published an article about Rxivist and our data.
  • 13 Jan 2019: The Rxivist preprint is live!