Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

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Title: Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
Authors: Kilpelainen, TO
Bentley, AR
Noordam, R
Sung, YJ
Schwander, K
Winkler, TW
Jakupovic, H
Chasman, DI
Manning, A
Ntalla, I
Aschard, H
Brown, MR
De las Fuentes, L
Franceschini, N
Guo, X
Vojinovic, D
Aslibekyan, S
Feitosa, MF
Kho, M
Musani, SK
Richard, M
Wang, H
Wang, Z
Bartz, TM
Bielak, LF
Campbell, A
Dorajoo, R
Fisher, V
Hartwig, FP
Horimoto, ARVR
Li, C
Lohman, KK
Marten, J
Sim, X
Smith, AV
Tajuddin, SM
Alver, M
Amini, M
Boissel, M
Chai, JF
Chen, X
Divers, J
Evangelou, E
Gao, C
Graff, M
Harris, SE
He, M
Hsu, F-C
Jackson, AU
Zhao, JH
Kraja, AT
Kuehnel, B
Laguzzi, F
Lyytikainen, L-P
Nolte, IM
Rauramaa, R
Riaz, M
Robino, A
Rueedi, R
Stringham, HM
Takeuchi, F
Van der Most, PJ
Varga, TV
Verweij, N
Ware, EB
Wen, W
Li, X
Yanek, LR
Amin, N
Arnett, DK
Boerwinkle, E
Brumat, M
Cade, B
Canouil, M
Chen, Y-DI
Concas, MP
Connell, J
De Mutsert, R
De Silva, HJ
De Vries, PS
Demirkan, A
Ding, J
Eaton, CB
Faul, JD
Friedlander, Y
Gabriel, KP
Ghanbari, M
Giulianini, F
Gu, CC
Gu, D
Harris, TB
He, J
Heikkinen, S
Heng, C-K
Hunt, SC
Ikram, MA
Jonas, JB
Koh, W-P
Komulainen, P
Krieger, JE
Kritchevsky, SB
Kutalik, Z
Kuusisto, J
Langefeld, CD
Langenberg, C
Launer, LJ
Leander, K
Lemaitre, RN
Lewis, CE
Liang, J
Alizadeh, BZ
Boezen, HM
Franke, L
Navis, G
Rots, M
Swertz, M
Wolffenbuttel, BHR
Wijmenga, C
Liu, J
Magi, R
Manichaikul, A
Meitinger, T
Metspalu, A
Milaneschi, Y
Mohlke, KL
Mosley, TH
Murray, AD
Nalls, MA
Nang, E-EK
Nelson, CP
Nona, S
Norris, JM
Nwuba, CV
O'Connell, J
Palmer, ND
Papanicolau, GJ
Pazoki, R
Pedersen, NL
Peters, A
Peyser, PA
Polasek, O
Porteous, DJ
Poveda, A
Raitakari, OT
Rich, SS
Risch, N
Robinson, JG
Rose, LM
Rudan, I
Schreiner, PJ
Scott, RA
Sidney, SS
Sims, M
Smith, JA
Snieder, H
Sofer, T
Starr, JM
Sternfeld, B
Strauch, K
Tang, H
Taylor, KD
Tsai, MY
Tuomilehto, J
Uitterlinden, AG
Van der Ende, MY
Van Heemst, D
Voortman, T
Waldenberger, M
Wennberg, P
Wilson, G
Xiang, Y-B
Yao, J
Yu, C
Yuan, J-M
Zhao, W
Zonderman, AB
Becker, DM
Boehnke, M
Bowden, DW
De Faire, U
Deary, IJ
Elliott, P
Esko, T
Freedman, BI
Froguel, P
Gasparini, P
Gieger, C
Kato, N
Laakso, M
Lakka, TA
Lehtimaaki, T
Magnusson, PKE
Oldehinkel, AJ
Penninx, BWJH
Samani, NJ
Shu, X-O
Van der Harst, P
Van Vliet-Ostaptchouk, JV
Vollenweider, P
Wagenknecht, LE
Wang, YX
Wareham, NJ
Weir, DR
Wu, T
Zheng, W
Zhu, X
Evans, MK
Franks, PW
Gudnason, V
Hayward, C
Horta, BL
Kelly, TN
Liu, Y
North, KE
Pereira, AC
Ridker, PM
Tai, ES
Van Dam, RM
Fox, ER
Kardia, SLR
Liu, C-T
Mook-Kanamori, DO
Province, MA
Redline, S
Van Duijn, CM
Rotter, JI
Kooperberg, CB
Gauderman, WJ
Psaty, BM
Rice, K
Munroe, PB
Fornage, M
Cupples, LA
Rotimi, CN
Morrison, AC
Rao, DC
Loos, RJF
Item Type: Journal Article
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.
Issue Date: 22-Jan-2019
Date of Acceptance: 7-Dec-2018
ISSN: 2041-1723
Publisher: Nature Research (part of Springer Nature)
Journal / Book Title: Nature Communications
Volume: 10
Copyright Statement: © 2019 The Author(s). Open Access. 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
Sponsor/Funder: Home Office
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: PG0484
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
African Continental Ancestry Group
Aged, 80 and over
Asian Continental Ancestry Group
Calcium-Binding Proteins
Cholesterol, HDL
Cholesterol, LDL
European Continental Ancestry Group
Genetic Loci
Genome-Wide Association Study
Hispanic Americans
LIM-Homeodomain Proteins
Lipid Metabolism
Membrane Proteins
Microtubule-Associated Proteins
Middle Aged
Muscle Proteins
Nerve Tissue Proteins
Transcription Factors
Young Adult
Lifelines Cohort Study
MD Multidisciplinary
Publication Status: Published
Article Number: 376 (2019)
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care

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