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Multi-ancestry analysis of gene-sleep interactions in 126,926 individuals identifies multiple novel blood lipid loci that contribute to our understanding of sleep-associated adverse blood lipid profile

By Raymond Noordam, Maxime M Bos, Heming Wang, Thomas W Winkler, Amy R Bentley, Tuomas O. Kilpeläinen, Paul S. de Vries, Yun Ju Sung, Karen Schwander, Brian E. Cade, Alisa Manning, Hugues Aschard, Michael R Brown, Han Chen, Nora Franceschini, Solomon K Musani, Melissa Richard, Dina Vojinovic, Stella Aslibekyan, Traci M Bartz, Lisa de las Fuentes, Mary Feitosa, Andrea R Horimoto, Marjan Ilkov, Minjung Kho, Aldi Kraja, Changwei Li, Elise Lim, Yongmei Liu, Dennis O. Mook-Kanamori, Tuomo Rankinen, Salman M Tajuddin, Ashley van der Spek, Zhe Wang, Jonathan Marten, Vincent Laville, Maris Alver, Evangelos Evangelou, Maria E Graff, Meian He, Brigitte Kühnel, Leo-Pekka Lyytikäinen, Pedro Marques-Vidal, Ilja M. Nolte, Nicholette D Palmer, Rainer Rauramaa, Xiao-Ou Shu, Harold Snieder, Stefan Weiss, Wanqing Wen, Lisa R. Yanek, Correa Adolfo, Christie Ballantyne, Larry Bielak, Nienke R Biermasz, Eric Boerwinkle, Niki Dimou, Gudny Eiriksdottir, Chuan Gao, Sina A. Gharib, Daniel J Gottlieb, José Haba-Rubio, Tamara B. Harris, Sami Heikkinen, Raphaël Heinzer, James E Hixson, Georg Homuth, M. Arfan Ikram, Pirjo Komulainen, Jose E Krieger, Jiwon Lee, Jingmin Liu, Kurt K Lohman, Annemarie I Luik, Reedik Mägi, Lisa W Martin, Thomas Meitinger, Andres Metspalu, Yuri Milaneschi, Mike A Nalls, Jeff O’Connell, Annette Peters, Patricia Peyser, Olli T. Raitakari, Alex P Reiner, Patrick CN Rensen, Treva K Rice, Stephen S Rich, Till Roenneberg, Jerome I. Rotter, Pamela J Schreiner, James Shikany, Stephen S Sidney, Mario Sims, Colleen M. Sitlani, Tamar Sofer, Konstantin Strauch, M. Swertz, Kent D. Taylor, André G. Uitterlinden, Cornelia Van Duijn, Henry Völzke, Melanie Waldenberger, Robert B Wallance, Ko Willems van Dijk, Caizheng Yu, Alan B Zonderman, Diane M. Becker, Paul Elliott, Tõnu Esko, Christian Gieger, Hans J. Grabe, Timo A. Lakka, Terho Lehtimäki, Lifelines Cohort Study, Kari E. North, Brenda WJH Penninx, Peter Vollenweider, Lynne E Wagenknecht, Tangchun Wu, Yong-Bing Xiang, Wei Zheng, Donna K. Arnett, Claude Bouchard, Michele K. Evans, Vilmundur Gudnason, Sharon Kardia, Tanika N Kelly, Stephen B. Kritchevsky, Ruth J.F. Loos, Alexandre C Pereira, Mike Province, Bruce M. Psaty, Charles Rotimi, Xiaofeng Zhu, Najaf Amin, L. Adrienne Cupples, Myriam Fornage, Ervin F Fox, Xiuqing Guo, W. James Gauderman, Kenneth Rice, Charles Kooperberg, Patricia B. Munroe, Ching-Ti Liu, Alanna C. Morrison, Dabeeru C Rao, Diana van Heemst, Susan Redline

Posted 25 Feb 2019
bioRxiv DOI: 10.1101/559393

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To provide new insights in the biology of sleep-associated adverse lipid profile, we conducted multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identified 49 novel lipid loci, and 10 additional novel lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identified new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The novel gene-sleep interactions had a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explained 4.25% of the variance in triglyceride concentration. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.

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