Citation
Kilpeläinen, Tuomas O.; Bentley, Amy R.; Noordam, Raymond; Sung, Yun J.; Schwander, Karen; Winkler, Thomas W.; Jakupović, Hermina; Chasman, Daniel I.; Manning, Alisa K.; & Ntalla, Ioanna, et al. (2019). Multi-Ancestry Study of Blood Lipid Levels Identifies Four Loci Interacting with Physical Activity. Nature Communications, 10, 376. PMCID: PMC6342931Abstract
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.URL
http://dx.doi.org/10.1038/s41467-018-08008-wReference Type
Journal ArticleYear Published
2019Journal Title
Nature CommunicationsAuthor(s)
Kilpeläinen, Tuomas O.Bentley, Amy R.
Noordam, Raymond
Sung, Yun J.
Schwander, Karen
Winkler, Thomas W.
Jakupović, Hermina
Chasman, Daniel I.
Manning, Alisa K.
Ntalla, Ioanna
Aschard, Hugues
Brown, Michael R.
de Las Fuentes, Lisa
Franceschini, Nora
Guo, Xiuqing
Vojinovic, Dina
Aslibekyan, Stella
Feitosa, Mary F.
Kho, Minjung
Musani, Solomon K.
Richard, Melissa A.
Wang, Heming
Wang, Zhe
Bartz, Traci M.
Bielak, Lawrence F.
Campbell, Archie
Dorajoo, Rajkumar
Fisher, Virginia A.
Hartwig, Fernando Pires
Horimoto, Andrea R. V. R.
Li, Changwei
Lohman, Kurt K.
Marten, Jonathan
Sim, Xueling
Smith, Albert V.
Tajuddin, Salman M.
Alver, Maris
Amini, Marzyeh
Boissel, Mathilde
Chai, Jin Fang
Chen, Xu
Divers, Jasmin
Evangelou, Evangelos
Gao, Chuan
Graff, Mariaelisa
Harris, Sarah E.
He, Meian
Hsu, Fang-Chi
Jackson, Anne U.
Zhao, Jing Hua
Kraja, Aldi T.
Kühnel, Brigitte
Laguzzi, Federica
Lyytikäinen, Leo-Pekka
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Rauramaa, Rainer
Riaz, Muhammad
Robino, Antonietta
Rueedi, Rico
Stringham, Heather M.
Takeuchi, Fumihiko
van der Most, Peter J.
Varga, Tibor V.
Verweij, Niek
Ware, Erin B.
Wen, Wanqing
Li, Xiaoyin
Yanek, Lisa R.
Amin, Najaf
Arnett, Donna K.
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Chen, Yii-Der Ida
Concas, Maria Pina
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de Mutsert, Renée
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Demirkan, Ayşe
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Heng, Chew-Kiat
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Ikram, M. Arfan
Jonas, Jost B.
Koh, Woon-Puay
Komulainen, Pirjo
Krieger, Jose E.
Kritchevsky, Stephen B.
Kutalik, Zoltán
Kuusisto, Johanna
Langefeld, Carl D.
Langenberg, Claudia
Launer, Lenore J.
Leander, Karin
Lemaitre, Rozenn N.
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Liang, Jingjing
Lifelines Cohort Study,
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Manichaikul, Ani
Meitinger, Thomas
Metspalu, Andres
Milaneschi, Yuri
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Schreiner, Pamela J.
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Sofer, Tamar
Starr, John M.
Sternfeld, Barbara
Strauch, Konstantin
Tang, Hua
Taylor, Kent D.
Tsai, Michael Y.
Tuomilehto, Jaakko
Uitterlinden, André G.
van der Ende, M. Yldau
van Heemst, Diana
Voortman, Trudy
Waldenberger, Melanie
Wennberg, Patrik
Wilson, Gregory, Sr.
Xiang, Yong-Bing
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Yuan, Jian-Min
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Zonderman, Alan B.
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Esko, Tõnu
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Gasparini, Paolo
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Lakka, Timo A.
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Magnusson, Patrik K. E.
Oldehinkel, Albertine J.
Penninx, Brenda W. J. H. W.
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van der Harst, Pim
Van Vliet-Ostaptchouk, Jana V.
Vollenweider, Peter
Wagenknecht, Lynne E.
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