Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

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. BartzLisa 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, Brenda W.J.H. Penninx

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct 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 identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.

Original languageEnglish
Article number5121
JournalNature Communications
Issue number1
Publication statusPublished - 1 Dec 2019

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