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

Kilpeläinen, Tuomas O.; Bentley, Amy R.; Noordam, Raymond; Sung, Yun Ju; Schwander, Karen; Winkler, Thomas W.; Jakupović, Hermina; Chasman, Daniel I.; Manning, Alisa; 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; Wang, Heming; Wang, Zhe; Bartz, Traci M.; Bielak, Lawrence F.; Campbell, Archie; Dorajoo, Rajkumar; Fisher, Virginia; Hartwig, Fernando P.; 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; Nolte, Ilja M.; 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.; Boerwinkle, Eric; Brumat, Marco; Cade, Brian; Canouil, Mickaël; Chen, Yii-Der Ida; Concas, Maria Pina; Connell, John; de Mutsert, Renée; de Silva, H. Janaka; de Vries, Paul S.; Demirkan, Ayşe; Ding, Jingzhong; Eaton, Charles B.; Faul, Jessica D.; Friedlander, Yechiel; Gabriel, Kelley P.; Ghanbari, Mohsen; Giulianini, Franco; Gu, Chi Charles; Gu, Dongfeng; Harris, Tamara B.; He, Jiang; Heikkinen, Sami; Heng, Chew-Kiat; Hunt, Steven C.; 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.; Lewis, Cora E.; Liang, Jingjing; Liu, Jianjun; Mägi, Reedik; Manichaikul, Ani; Meitinger, Thomas; Metspalu, Andres; Milaneschi, Yuri; Mohlke, Karen L.; Mosley, Thomas H.; Murray, Alison D.; Nalls, Mike A.; Nang, Ei-Ei Khaing; Nelson, Christopher P.; Nona, Sotoodehnia; Norris, Jill M.; Nwuba, Chiamaka Vivian; O’Connell, Jeff; Palmer, Nicholette D.; Papanicolau, George J.; Pazoki, Raha; Pedersen, Nancy L.; Peters, Annette; Peyser, Patricia A.; Polasek, Ozren; Porteous, David J.; Poveda, Alaitz; Raitakari, Olli T.; Rich, Stephen S.; Risch, Neil; Robinson, Jennifer G.; Rose, Lynda M.; Rudan, Igor; Schreiner, Pamela J.; Scott, Robert A.; Sidney, Stephen S.; Sims, Mario; Smith, Jennifer A.; Snieder, Harold; 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; Xiang, Yong-Bing; Yao, Jie; Yu, Caizheng; Yuan, Jian-Min; Zhao, Wei; Zonderman, Alan B.; Becker, Diane M.; Boehnke, Michael; Bowden, Donald W.; de Faire, Ulf; Deary, Ian J.; Elliott, Paul; Esko, Tõnu; Freedman, Barry I.; Froguel, Philippe; Gasparini, Paolo; Gieger, Christian; Kato, Norihiro; Laakso, Markku; Lakka, Timo A.; Lehtimäki, Terho; Magnusson, Patrik K. E.; Oldehinkel, Albertine J.; Penninx, Brenda W. J. H.; Samani, Nilesh J.; Shu, Xiao-Ou; van der Harst, Pim; Van Vliet-Ostaptchouk, Jana V.; Vollenweider, Peter; Wagenknecht, Lynne E.; Wang, Ya X.; Wareham, Nicholas J.; Weir, David R.; Wu, Tangchun; Zheng, Wei; Zhu, Xiaofeng; Evans, Michele K.; Franks, Paul W.; Gudnason, Vilmundur; Hayward, Caroline; Horta, Bernardo L.; Kelly, Tanika N.; Liu, Yongmei; North, Kari E.; Pereira, Alexandre C.; Ridker, Paul M.; Tai, E. Shyong; van Dam, Rob M.; Fox, Ervin R.; Kardia, Sharon L. R.; Liu, Ching-Ti; Mook-Kanamori, Dennis O.; Province, Michael A.; Redline, Susan; van Duijn, Cornelia M.; Rotter, Jerome I.; Kooperberg, Charles B.; Gauderman, W. James; Psaty, Bruce M.; Rice, Kenneth; Munroe, Patricia B.; Fornage, Myriam; Cupples, L. Adrienne; Rotimi, Charles N.; Morrison, Alanna C.; Rao, Dabeeru C. and Loos, Ruth J. F. (2019). Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity. Nature Communications, 10(1), article no. 376.

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DOI (Digital Object Identifier) Link: https://doi.org/10.1038/s41467-018-08008-w
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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.

Item Type: Journal Item
Copyright Holders: 2019 The Author(s)
ISSN: 2041-1723
Keywords: Cardiovascular genetics; Dyslipidaemias; Genome-wide association studies
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Mathematics and Statistics
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 68067
Depositing User: Muhammad Riaz
Date Deposited: 14 Nov 2019 09:59
Last Modified: 29 Jun 2020 12:29
URI: http://oro.open.ac.uk/id/eprint/68067
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