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Multi-ancestry genome-wide gene–smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

Bentley, Amy R.; Sung, Yun J.; Brown, Michael R.; Winkler, Thomas W.; Kraja, Aldi T.; Ntalla, Ioanna; Schwander, Karen; Chasman, Daniel I.; Lim, Elise; Deng, Xuan; Guo, Xiuqing; Liu, Jingmin; Lu, Yingchang; Cheng, Ching-Yu; Sim, Xueling; Vojinovic, Dina; Huffman, Jennifer E.; Musani, Solomon K.; Li, Changwei; Feitosa, Mary F.; Richard, Melissa A.; Noordam, Raymond; Baker, Jenna; Chen, Guanjie; Aschard, Hugues; Bartz, Traci M.; Ding, Jingzhong; Dorajoo, Rajkumar; Manning, Alisa K.; Rankinen, Tuomo; Smith, Albert V.; Tajuddin, Salman M.; Zhao, Wei; Graff, Mariaelisa; Alver, Maris; Boissel, Mathilde; Chai, Jin Fang; Chen, Xu; Divers, Jasmin; Evangelou, Evangelos; Gao, Chuan; Goel, Anuj; Hagemeijer, Yanick; Harris, Sarah E.; Hartwig, Fernando P.; He, Meian; Horimoto, Andrea R. V. R.; Hsu, Fang-Chi; Hung, Yi-Jen; Jackson, Anne U.; Kasturiratne, Anuradhani; Komulainen, Pirjo; Kühnel, Brigitte; Leander, Karin; Lin, Keng-Hung; Luan, Jian’an; Lyytikäinen, Leo-Pekka; Matoba, Nana; Nolte, Ilja M.; Pietzner, Maik; Prins, Bram; Riaz, Muhammad; Robino, Antonietta; Said, M. Abdullah; Schupf, Nicole; Scott, Robert A.; Sofer, Tamar; Stancáková, Alena; Takeuchi, Fumihiko; Tayo, Bamidele O.; van der Most, Peter J.; Varga, Tibor V.; Wang, Tzung-Dau; Wang, Yajuan; Ware, Erin B.; Wen, Wanqing; Xiang, Yong-Bing; Yanek, Lisa R.; Zhang, Weihua; Zhao, Jing Hua; Adeyemo, Adebowale; Afaq, Saima; Amin, Najaf; Amini, Marzyeh; Arking, Dan E.; Arzumanyan, Zorayr; Aung, Tin; Ballantyne, Christie; Barr, R. Graham; Bielak, Lawrence F.; Boerwinkle, Eric; Bottinger, Erwin P.; Broeckel, Ulrich; Brown, Morris; Cade, Brian E.; Campbell, Archie; Canouil, Mickaël; Charumathi, Sabanayagam; Chen, Yii-Der Ida; Christensen, Kaare; Concas, Maria Pina; Connell, John M.; de las Fuentes, Lisa; de Silva, H. Janaka; de Vries, Paul S.; Doumatey, Ayo; Duan, Qing; Eaton, Charles B.; Eppinga, Ruben N.; Faul, Jessica D.; Floyd, James S.; Forouhi, Nita G.; Forrester, Terrence; Friedlander, Yechiel; Gandin, Ilaria; Gao, He; Ghanbari, Mohsen; Gharib, Sina A.; Gigante, Bruna; Giulianini, Franco; Grabe, Hans J.; Gu, C. Charles; Harris, Tamara B.; Heikkinen, Sami; Heng, Chew-Kiat; Hirata, Makoto; Hixson, James E.; Ikram, M. Arfan; Jia, Yucheng; Joehanes, Roby; Johnson, Craig; Jonas, Jost Bruno; Justice, Anne E.; Katsuya, Tomohiro; Khor, Chiea Chuen; Kilpeläinen, Tuomas O.; Koh, Woon-Puay; Kolcic, Ivana; Kooperberg, Charles; Krieger, Jose E.; Kritchevsky, Stephen B.; Kubo, Michiaki; Kuusisto, Johanna; Lakka, Timo A.; Langefeld, Carl D.; Langenberg, Claudia; Launer, Lenore J.; Lehne, Benjamin; Lewis, Cora E.; Li, Yize; Liang, Jingjing; Lin, Shiow; Liu, Ching-Ti; Liu, Jianjun; Liu, Kiang; Loh, Marie; Lohman, Kurt K.; Louie, Tin; Luzzi, Anna; Mägi, Reedik; Mahajan, Anubha; Manichaikul, Ani W.; McKenzie, Colin A.; Meitinger, Thomas; Metspalu, Andres; Milaneschi, Yuri; Milani, Lili; Mohlke, Karen L.; Momozawa, Yukihide; Morris, Andrew P.; Murray, Alison D.; Nalls, Mike A.; Nauck, Matthias; Nelson, Christopher P.; North, Kari E.; O’Connell, Jeffrey R.; Palmer, Nicholette D.; Papanicolau, George J.; Pedersen, Nancy L.; Peters, Annette; Peyser, Patricia A.; Polasek, Ozren; Poulter, Neil; Raitakari, Olli T.; Reiner, Alex P.; Renström, Frida; Rice, Treva K.; Rich, Stephen S.; Robinson, Jennifer G.; Rose, Lynda M.; Rosendaal, Frits R.; Rudan, Igor; Schmidt, Carsten O.; Schreiner, Pamela J.; Scott, William R.; Sever, Peter; Shi, Yuan; Sidney, Stephen; Sims, Mario; Smith, Jennifer A.; Snieder, Harold; Starr, John M.; Strauch, Konstantin; Stringham, Heather M.; Tan, Nicholas Y. Q.; Tang, Hua; Taylor, Kent D.; Teo, Yik Ying; Tham, Yih Chung; Tiemeier, Henning; Turner, Stephen T.; Uitterlinden, André G.; van Heemst, Diana; Waldenberger, Melanie; Wang, Heming; Wang, Lan; Wang, Lihua; Wei, Wen Bin; Williams, Christine A.; Wilson, Gregory; Wojczynski, Mary K.; Yao, Jie; Young, Kristin; Yu, Caizheng; Yuan, Jian-Min; Zhou, Jie; Zonderman, Alan B.; Becker, Diane M.; Boehnke, Michael; Bowden, Donald W.; Chambers, John C.; Cooper, Richard S.; de Faire, Ulf; Deary, Ian J.; Elliott, Paul; Esko, Tõnu; Farrall, Martin; Franks, Paul W.; Freedman, Barry I.; Froguel, Philippe; Gasparini, Paolo; Gieger, Christian; Horta, Bernardo L.; Juang, Jyh-Ming Jimmy; Kamatani, Yoichiro; Kammerer, Candace M.; Kato, Norihiro; Kooner, Jaspal S.; Laakso, Markku; Laurie, Cathy C.; Lee, I-Te; Lehtimäki, Terho; Magnusson, Patrik K. E.; Oldehinkel, Albertine J.; Penninx, Brenda W. J. H.; Pereira, Alexandre C.; Rauramaa, Rainer; Redline, Susan; Samani, Nilesh J.; Scott, James; Shu, Xiao-Ou; van der Harst, Pim; Wagenknecht, Lynne E.; Wang, Jun-Sing; Wang, Ya Xing; Wareham, Nicholas J.; Watkins, Hugh; Weir, David R.; Wickremasinghe, Ananda R.; Wu, Tangchun; Zeggini, Eleftheria; Zheng, Wei; Bouchard, Claude; Evans, Michele K.; Gudnason, Vilmundur; Kardia, Sharon L. R.; Liu, Yongmei; Psaty, Bruce M.; Ridker, Paul M.; van Dam, Rob M.; Mook-Kanamori, Dennis O.; Fornage, Myriam; Province, Michael A.; Kelly, Tanika N.; Fox, Ervin R.; Hayward, Caroline; van Duijn, Cornelia M.; Tai, E. Shyong; Wong, Tien Yin; Loos, Ruth J. F.; Franceschini, Nora; Rotter, Jerome I.; Zhu, Xiaofeng; Bierut, Laura J.; Gauderman, W. James; Rice, Kenneth; Munroe, Patricia B.; Morrison, Alanna C.; Rao, Dabeeru C.; Rotimi, Charles N. and Cupples, L. Adrienne (2019). Multi-ancestry genome-wide gene–smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids. Nature Genetics, 51(4) pp. 636–648.

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DOI (Digital Object Identifier) Link: https://doi.org/10.1038/s41588-019-0378-y
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Abstract

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene–smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.

Item Type: Journal Item
Copyright Holders: Nature Genetics
ISSN: 1061-4036
Keywords: Cardiovascular diseases; Genome-wide association studies; Genomics
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Mathematics and Statistics
Faculty of Science, Technology, Engineering and Mathematics (STEM)
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Item ID: 68066
Depositing User: Muhammad Riaz
Date Deposited: 14 Nov 2019 10:20
Last Modified: 10 Dec 2019 01:29
URI: http://oro.open.ac.uk/id/eprint/68066
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