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

Amy R Bentley (Corresponding Author), 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, Fang-Chi Hsu, Yi-Jen Hung, Alison D Murray, COGENT-Kidney Consortium

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70 Citations (Scopus)
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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 novel loci, some of which were detected only because the association differed by smoking status. Additionally, we demonstrated 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
Number of pages13
JournalNature Genetics
Issue number4
Early online date29 Mar 2019
Publication statusPublished - Apr 2019

Bibliographical note

This project was largely supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305) and by the Intramural Research Program of the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (Z01HG200362). Anne E Justice was supported in part by the American Heart Association (13POST16500011) and NIH (2T32HL007055, K99HL130580). Study-specific acknowledgments appear in the Supplementary Information.

All summary results will be made available in dbGaP (phs000930.v7.p1).


  • cardiovascular diseases
  • genome wide association studies
  • genomics


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