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
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 CN , 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 , Duijn Cornelia M van , Völzke Henry , Waldenberger Melanie , Wallance Robert B , Dijk Ko Willems van , Yu Caizheng , Zonderman Alan B , Becker Diane M , Elliott Paul , Esko Tõnu , Gieger Christian , Grabe Hans J , Lakka Timo A , Lehtimäki Terho , Study Lifelines Cohort , North Kari E , Penninx Brenda WJH , 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 JF , 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 , Heemst Diana van , Redline Susan 
Published: February 2019

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 asLPLandPCSK9. 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.