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

Raymond Noordam (1) , Maxime M. Bos (1) , Heming Wang (2) , Thomas W. Winkler (3) , Amy R. Bentley (4) , Tuomas O. Kilpeläinen (5, 6) , Paul S. de Vries (7) , Yun Ju Sung (8) , Karen Schwander (8) , Brian E. Cade (2) , Alisa Manning (9, 10) , Hugues Aschard (11, 12) , Michael R. Brown (7) , Han Chen (7) , Nora Franceschini (13) , Solomon K. Musani (14) , Melissa Richard (7) , Dina Vojinovic (15) , Stella Aslibekyan (16) , Traci M. Bartz (17) , Lisa de Las Fuentes (8) , Mary Feitosa (8) , Andrea R. Horimoto (18) , Marjan Ilkov (19) , Minjung Kho (20) , Aldi Kraja (8) , Changwei Li (21) , Elise Lim (22) , Yongmei Liu (23) , Dennis O. Mook-Kanamori (1) , Tuomo Rankinen (24) , Salman M. Tajuddin (4) , Ashley van Der Spek (15) , Zhe Wang (7) , Jonathan Marten (25) , Vincent Laville (12) , Maris Alver (26) , Evangelos Evangelou (27, 28) , Maria E. Graff (13) , Meian He (29) , Brigitte Kühnel (30) , Leo-Pekka Lyytikäinen (31, 32) , Pedro Marques-Vidal (33) , Ilja M. Nolte (34) , Nicholette Palmer , Rainer Rauramaa , Xiao-Ou Shu , Harold Snieder (34) , Stefan Weiss , Wanqing Wen , Lisa Yanek , Correa Adolfo (14) , Christie Ballantyne , Larry Bielak (20) , Nienke Biermasz , Eric Boerwinkle (7) , Niki Dimou (28) , Gudny Eiriksdottir (19) , Chuan Gao , Sina Gharib , Daniel J. Gottlieb (2, 10) , José Haba-Rubio , Tamara Harris (2) , Sami Heikkinen , Raphaël Heinzer , James E. Hixson (7) , Georg Homuth , M. Arfan Ikram (15) , Pirjo Komulainen , Jose E. Krieger (18) , Jiwon Lee (2) , Jingmin Liu , Kurt Lohman , Annemarie I. Luik (15) , Reedik Mägi (26) , Lisa Martin , Thomas Meitinger , Andres Metspalu (26) , Yuri Milaneschi , Mike Nalls , Jeff O'Connell , Annette Peters (30) , Patricia Peyser (20) , Olli Raitakari , Alex Reiner , Patrick Rensen , Treva K. Rice (8) , Stephen Rich , Till Roenneberg , Jerome Rotter , Pamela Schreiner , James Shikany , Stephen Sidney , Mario Sims (14) , Colleen Sitlani , Tamar Sofer , Konstantin Strauch , Morris Swertz , Kent Taylor , André G. Uitterlinden (15) , Cornelia M. van Duijn (15) , Henry Völzke , Melanie Waldenberger (30) , Robert Wallance , Ko Willems van Dijk , Caizheng Yu (29) , Alan Zonderman , Diane Becker , Paul Elliott (26) , Tõnu Esko (26) , Christian Gieger (30) , Hans Grabe , Timo Lakka , Terho Lehtimäki (31, 32) , Kari E. North (13) , Brenda Penninx , Peter Vollenweider (33) , Lynne Wagenknecht , Tangchun Wu (29) , Yong-Bing Xiang , Wei Zheng , Donna Arnett , Claude Bouchard (24) , Michele K. Evans (4) , Vilmundur Gudnason (19) , Sharon Kardia (20) , Tanika Kelly , Stephen Kritchevsky , Ruth Loos , Alexandre C. Pereira (18) , Mike Province (8) , Bruce Psaty , Charles Rotimi (4) , Xiaofeng Zhu , Najaf Amin (15) , L. Adrienne Cupples (22) , Myriam Fornage (7) , Ervin Fox , Xiuqing Guo , W. James Gauderman , Kenneth Rice , Charles Kooperberg , Patricia Munroe , Ching-Ti Liu (22) , Alanna C. Morrison (7) , Dabeeru C. Rao (8) , Diana van Heemst (1) , Susan Redline (2)

1 Leiden University Medical Center (LUMC)
2 BWH - Brigham & Women’s Hospital [Boston]
3 UR - Universität Regensburg
4 NIH - National Institutes of Health [Bethesda]
5 UCPH - University of Copenhagen = Københavns Universitet
6 MSSM - Icahn School of Medicine at Mount Sinai [New York]
7 UTHealth - The University of Texas Health Science Center at Houston
8 Washington University School of Medicine in St. Louis
9 Massachusetts General Hospital [Boston]
10 HMS - Harvard Medical School [Boston]
11 Harvard T.H. Chan School of Public Health
12 C3BI - Centre de Bioinformatique, Biostatistique et Biologie Intégrative
13 UNC - University of North Carolina [Chapel Hill]
14 UMMC - University of Mississippi Medical Center
15 Erasmus MC - Erasmus University Medical Center [Rotterdam]
16 UAB - University of Alabama at Birmingham [ Birmingham]
17 University of Washington [Seattle]
18 FMUSP - Universidade de São Paulo Medical School
19 IHA - Icelandic Heart Association [Kopavogur, Iceland]
20 University of Michigan [Ann Arbor]
21 University of Georgia [USA]
22 School of Public Health [Boston]
23 Wake Forest University
24 Pennington Biomedical Research Center
25 University of Edinburgh
26 University of Tartu
27 Imperial College London
28 University of Ioannina
29 HUST - Huazhong University of Science and Technology [Wuhan]
30 Helmholtz Zentrum München = German Research Center for Environmental Health
31 Fimlab Laboratories [Tampere, Finland]
32 University of Tampere [Finland]
33 Lausanne University Hospital
34 University of Groningen [Groningen]

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.

Domains: Human genetics; Santé publique et épidémiologie; Methodology [stat.ME]; Applications [stat.AP]; Bioinformatics [q-bio.QM]

Raymond Noordam, Maxime M. Bos, Heming Wang, Thomas W. Winkler, Amy R. Bentley, et al.. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration. Nature Communications, 2019, 10 (1), pp.5121. ⟨10.1038/s41467-019-12958-0⟩. ⟨pasteur-03278561⟩