Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration
Authors: Noordam Raymond , Bos Maxime M. , Wang Heming , Winkler Thomas W. , Bentley Amy R. , Kilpeläinen Tuomas O. , de Vries Paul S. , Sung Yun Ju , Schwander Karen , Cade Brian E. , Manning Alisa , Aschard Hugues , Brown Michael R. , Chen Han , Franceschini Nora , Musani Solomon K. , Richard Melissa , Vojinovic Dina , Aslibekyan Stella , Bartz Traci M. , de las Fuentes Lisa , Feitosa Mary , Horimoto Andrea R. , Ilkov Marjan , Kho Minjung , Kraja Aldi , Li Changwei , Lim Elise , Liu Yongmei , Mook-Kanamori Dennis O. , Rankinen Tuomo , Tajuddin Salman M. , van der Spek Ashley , Wang Zhe , Marten Jonathan , Laville Vincent , Alver Maris , Evangelou Evangelos , Graff Maria E. , He Meian , Kühnel Brigitte , Lyytikäinen Leo-Pekka , Marques-Vidal Pedro , Nolte Ilja M. , Palmer Nicholette D. , Rauramaa Rainer , Shu Xiao-Ou , Snieder Harold , Weiss Stefan , Wen Wanqing , Yanek Lisa R. , Adolfo Correa , Ballantyne Christie , Bielak Larry , Biermasz Nienke R. , Boerwinkle Eric , Dimou Niki , Eiriksdottir Gudny , Gao Chuan , Gharib Sina A. , Gottlieb Daniel J. , Haba-Rubio José , Harris Tamara B. , Heikkinen Sami , Heinzer Raphaël , Hixson James E. , Homuth Georg , Ikram M. Arfan , Komulainen Pirjo , Krieger Jose E. , Lee Jiwon , Liu Jingmin , Lohman Kurt K. , Luik Annemarie I. , Mägi Reedik , Martin Lisa W. , Meitinger Thomas , Metspalu Andres , Milaneschi Yuri , Nalls Mike A. , O’Connell Jeff , Peters Annette , Peyser Patricia , Raitakari Olli T. , Reiner Alex P. , Rensen Patrick C. N. , Rice Treva K. , Rich Stephen S. , Roenneberg Till , Rotter Jerome I. , Schreiner Pamela J. , Shikany James , Sidney Stephen S. , Sims Mario , Sitlani Colleen M. , Sofer Tamar , Strauch Konstantin , Swertz Morris A. , Taylor Kent D. , Uitterlinden André G. , van Duijn Cornelia M. , Völzke Henry , Waldenberger Melanie , Wallance Robert B. , van Dijk Ko Willems , Yu Caizheng , Zonderman Alan B. , Becker Diane M. , Elliott Paul , Esko Tõnu , Gieger Christian , Grabe Hans J. , Lakka Timo A. , Lehtimäki Terho , North Kari E. , Penninx Brenda W. J. H. , Vollenweider Peter , Wagenknecht Lynne E. , Wu Tangchun , Xiang Yong-Bing , Zheng Wei , Arnett Donna K. , Bouchard Claude , Evans Michele K. , Gudnason Vilmundur , Kardia Sharon , Kelly Tanika N. , Kritchevsky Stephen B. , Loos Ruth J. F. , Pereira Alexandre C. , Province Mike , Psaty Bruce M. , Rotimi Charles , Zhu Xiaofeng , Amin Najaf , Cupples L. Adrienne , Fornage Myriam , Fox Ervin F. , Guo Xiuqing , Gauderman W. James , Rice Kenneth , Kooperberg Charles , Munroe Patricia B. , Liu Ching-Ti , Morrison Alanna C. , Rao Dabeeru C. , van Heemst Diana , Redline Susan 
Published: November 2019

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 asLPLandPCSK9. 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.