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

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

Year of Publication
2019
Journal
Nature genetics
Volume
51
Issue
4
Number of Pages
636-648
Date Published
12/2019
ISSN Number
1546-1718
DOI
10.1038/s41588-019-0378-y
Alternate Journal
Nat. Genet.
PMID
30926973
PMCID
PMC6467258
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