Authors

Tuomas O. Kilpeläinen, University of Copenhagen, Denmark
Amy R. Bentley, National Human Genome Research Institute
Raymond Noordam, Leiden University, The Netherlands
Yun Ju Sung, Washington University in St. Louis
Karen Schwander, Washington University in St. Louis
Thomas W. Winkler, University of Regensburg, Germany
Hermina Jakupović, University of Copenhagen, Denmark
Daniel I. Chasman, Harvard University
Alisa Manning, Massachusetts General Hospital
Ioanna Ntalla, Queen Mary University of London, UK
Hugues Aschard, Harvard University
Michael R. Brown, The University of Texas Health Science Center at Houston
Lisa de las Fuentes, Washington University in St. Louis
Nora Franceschini, University of North Carolina at Chapel Hill
Xiuqing Guo, Harbor-UCLA Medical Center
Dina Vojinovic, Erasmus University, The Netherlands
Stella Aslibekyan, University of Alabama at Birmingham
Mary F. Feitosa, Washington University in St. Louis
Minjung Kho, University of Michigan - Ann Arbor
Solomon K. Musani, University of Mississippi
Melissa Richard, The University of Texas Health Science Center at Houston
Heming Wang, Brigham and Women’s Hospital
Zhe Wang, The University of Texas Health Science Center at Houston
Traci M. Bartz, University of Washington
Lawrence F. Bielak, University of Michigan - Ann Arbor
Archie Campbell, University of Edinburgh, UK
Rajkumar Dorajoo, Agency for Science Technology and Research, Singapore
Virginia Fisher, Boston University
Fernando P. Hartwig, Federal University of Pelotas, Brazil
Andrea R. V. R. Horimoto, University of São Paulo, Brazil
Donna K. Arnett, University of KentuckyFollow

Abstract

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.

Document Type

Article

Publication Date

1-22-2019

Notes/Citation Information

Published in Nature Communications, v. 10, article no. 376, p. 1-11.

© The Author(s) 2019

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Due to the large number of authors, only the first 30 and the authors affiliated with the University of Kentucky are listed in the author section above. For the complete list of authors, please download this article or visit:

Digital Object Identifier (DOI)

https://doi.org/10.1038/s41467-018-08008-w

Funding Information

The present work was largely supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305).

Related Content

The meta-analysis summary results are available for download on the CHARGE dbGaP website under accession phs000930.

Supplementary Information accompanies this paper at https://doi.org/10.1038/s41467- 018-08008-w.

41467_2018_8008_MOESM1_ESM.pdf (1041 kB)
Supplementary Information

41467_2018_8008_MOESM2_ESM.pdf (339 kB)
Peer Review File

41467_2018_8008_MOESM3_ESM.pdf (19 kB)
Description of Additional Supplementary Files

41467_2018_8008_MOESM4_ESM.xlsx (15 kB)
Supplementary Data 1

41467_2018_8008_MOESM5_ESM.xlsx (24 kB)
Supplementary Data 2

41467_2018_8008_MOESM6_ESM.xlsx (26 kB)
Supplementary Data 3

41467_2018_8008_MOESM7_ESM.xlsx (34 kB)
Supplementary Data 4

41467_2018_8008_MOESM8_ESM.xlsx (30 kB)
Supplementary Data 5

41467_2018_8008_MOESM9_ESM.xlsx (27 kB)
Supplementary Data 6

41467_2018_8008_MOESM10_ESM.xlsx (31 kB)
Supplementary Data 7

41467_2018_8008_MOESM11_ESM.xlsx (25 kB)
Supplementary Data 8

41467_2018_8008_MOESM12_ESM.xlsx (24 kB)
Supplementary Data 9

41467_2018_8008_MOESM13_ESM.xlsx (24 kB)
Supplementary Data 10

Share

COinS