Multi-Ancestry Sleep-by-SNP Interaction Analysis in 126,926 Individuals Reveals Lipid Loci Stratified by Sleep Duration

Authors

Raymond Noordam, Leiden University, The Netherlands
Maxime M. Bos, Leiden University, The Netherlands
Heming Wang, Harvard University
Thomas W. Winkler, University of Regensburg, Germany
Amy R. Bentley, National Human Genome Research Institute
Tuomas O. Kilpeläinen, University of Copenhagen, Denmark
Paul S. de Vries, The University of Texas Health Science Center at Houston
Yun Ju Sung, Washington University
Karen Schwander, Washington University
Brian E. Cade, Harvard University
Alisa Manning, Harvard University
Hugues Aschard, Harvard University
Michael R. Brown, The University of Texas Health Science Center at Houston
Han Chen, The University of Texas Health Science Center at Houston
Nora Franceschini, University of North Carolina, Chapel Hill
Solomon K. Musani, University of Mississippi
Melissa Richard, The University of Texas Health Science Center at Houston
Dina Vojinovic, Erasmus University, The Netherlands
Stella Aslibekyan, University of Alabama at Birmingham
Traci M. Bartz, University of Washington
Donna K. Arnett, University of KentuckyFollow

Abstract

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.

Document Type

Article

Publication Date

11-12-2019

Notes/Citation Information

Published in Nature Communications, v. 10, article no. 5121.

© The Author(s) 2019

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The first 20 authors and the author from the University of Kentucky are shown on the author list above. Please refer to the downloaded document for the complete author list.

Digital Object Identifier (DOI)

https://doi.org/10.1038/s41467-019-12958-0

Funding Information

This project was supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305). This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Tuomas O. Kilpeläinen was supported by the Danish Council for Independent Research (DFF–6110-00183) and the Novo Nordisk Foundation (NNF18CC0034900, NNF17OC0026848 and NNF15CC0018486). Diana van Heemst was supported by the European Commission funded project HUMAN (Health-2013-INNOVATION-1-602757). Susan Redline was supported in part by NIH R35HL135818 and HL11338. Study-specific acknowledgements can be found in the Supplementary Notes 2 and 4. The data on coronary artery disease have been contributed by the Myocardial Infarction Genetics and CARDIoGRAM investigators, and have been downloaded from www.CARDIOGRAMPLUSC4D.ORG.

Related Content

Due to restrictions in the written informed consent and local regulations, no individual genotype-level data could be shared that were part of this project. Summary results files from both the trans-ancestry and European meta-analyses are available to the public via the CHARGE (Cohorts for Heart and Ageing Research in Genomics Epidemiology) dbGaP summary site (phs000930 [https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000930.v1.p1]). We acknowledge the use of publically available data sources for summary-based statistics, which includes the gTex portal [https://gtexportal.org/home/], Nealelab [http://www.nealelab.is/uk-biobank/], Sleep Disorder Genetics [http://sleepdisordergenetics.org/] and the CARDIoGRAMplusC4D consortium [http://www.cardiogramplusc4d.org].

Repository Citation

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.; and Arnett, Donna K., "Multi-Ancestry Sleep-by-SNP Interaction Analysis in 126,926 Individuals Reveals Lipid Loci Stratified by Sleep Duration" (2019). Epidemiology and Environmental Health Faculty Publications. 79.
https://uknowledge.uky.edu/epidemiology_facpub/79