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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,
Morris A. Swertz,
Kent D Taylor,
André G. Uitterlinden,
Cornelia M. 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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