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

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. FeitosaMelissa A. Richard, Raymond Noordam, Jenna Baker, Guanjie Chen, Hugues Aschard, Traci M. Bartz, Jingzhong Ding, Rajkumar Dorajoo, Alisa K. Manning, Tuomo Rankinen, Albert V. Smith, 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. V. R. Horimoto, Yuri Milaneschi, Jian-Min Yuan, Brenda W. J. H. Penninx, COGENT-Kidney Consortium, EPIC-InterAct Consortium, Understanding Society Scientific group, Lifelines Cohort, 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 Wareham, H. 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, Caroline Hayward, Cornelia M. van Duijn, E-Shyong Tai, Tien Yin Wong, Ruth J. F. Loos, Nora Franceschini, Jerome I. Rotter, Xiaofeng Zhu, Laura J. Bierut, W. James Gauderman, Kenneth M. Rice, Patricia B. Munroe, Alanna C. Morrison, Dabeeru C. Rao, Charles N. Rotimi, L. Adrienne Cupples

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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.
Original languageEnglish
Pages (from-to)636-648
JournalNature Genetics
Volume51
Issue number4
DOIs
Publication statusPublished - 1 Apr 2019

Cite this

Bentley, A. R., Sung, Y. J., Brown, M. R., Winkler, T. W., Kraja, A. T., Ntalla, I., ... Cupples, L. A. (2019). Multi-ancestry genome-wide gene–smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids. Nature Genetics, 51(4), 636-648. https://doi.org/10.1038/s41588-019-0378-y