Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies novel 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 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 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

doi:10.1038/s41588-019-0378-y

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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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 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 language	English
Pages (from-to)	636-648
Number of pages	13
Journal	Nature Genetics
Volume	51
Issue number	4
Early online date	29 Mar 2019
DOIs	https://doi.org/10.1038/s41588-019-0378-y
Publication status	Published - 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).

Keywords

cardiovascular diseases
genome wide association studies
genomics
ENVIRONMENT INTERACTION
METAANALYSIS
CHOLESTEROL
CIGARETTES
VARIANTS
SUSCEPTIBILITY
NICOTINE METABOLISM
RISK LOCI
GENOTYPE IMPUTATION
ARCHITECTURE

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Accepted ManuscriptAccepted author manuscript, 1.39 MBLicence: Other

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Bentley, A. R., Sung, Y. J., Brown, M. R., Winkler, T. W., Kraja, A. T., Ntalla, I., Schwander, K., Chasman, D. I., Lim, E., Deng, X., Guo, X., Liu, J., Lu, Y., Cheng, C.-Y., Sim, X., Vojinovic, D., Huffman, J. E., Musani, S. K., Li, C., ... COGENT-Kidney Consortium (2019). Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies novel loci associated with serum lipids. Nature Genetics, 51(4), 636-648. https://doi.org/10.1038/s41588-019-0378-y

Bentley, AR, Sung, YJ, Brown, MR, Winkler, TW, Kraja, AT, Ntalla, I, Schwander, K, Chasman, DI, Lim, E, Deng, X, Guo, X, Liu, J, Lu, Y, Cheng, C-Y, Sim, X, Vojinovic, D, Huffman, JE, Musani, SK, Li, C, Feitosa, MF, Richard, MA, Noordam, R, Baker, J, Chen, G, Aschard, H, Bartz, TM, Ding, J, Dorajoo, R, Manning, AK, Rankinen, T, Smith, AV, Tajuddin, SM, Zhao, W, Graff, M, Alver, M, Boissel, M, Chai, JF, Chen, X, Divers, J, Evangelou, E, Gao, C, Goel, A, Hagemeijer, Y, Harris, SE, Hartwig, FP, He, M, Horimoto, ARVR, Hsu, F-C, Hung, Y-J, Murray, AD & COGENT-Kidney Consortium 2019, 'Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies novel loci associated with serum lipids', Nature Genetics, vol. 51, no. 4, pp. 636-648. 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 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.",

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AU - Bentley, Amy R

AU - Sung, Yun J

AU - Brown, Michael R

AU - Winkler, Thomas W

AU - Kraja, Aldi T

AU - Ntalla, Ioanna

AU - Schwander, Karen

AU - Chasman, Daniel I

AU - Lim, Elise

AU - Deng, Xuan

AU - Guo, Xiuqing

AU - Liu, Jingmin

AU - Lu, Yingchang

AU - Cheng, Ching-Yu

AU - Sim, Xueling

AU - Vojinovic, Dina

AU - Huffman, Jennifer E

AU - Musani, Solomon K

AU - Li, Changwei

AU - Feitosa, Mary F

AU - Richard, Melissa A

AU - Noordam, Raymond

AU - Baker, Jenna

AU - Chen, Guanjie

AU - Aschard, Hugues

AU - Bartz, Traci M

AU - Ding, Jingzhong

AU - Dorajoo, Rajkumar

AU - Manning, Alisa K

AU - Rankinen, Tuomo

AU - Smith, Albert V

AU - Tajuddin, Salman M

AU - Zhao, Wei

AU - Graff, Mariaelisa

AU - Alver, Maris

AU - Boissel, Mathilde

AU - Chai, Jin Fang

AU - Chen, Xu

AU - Divers, Jasmin

AU - Evangelou, Evangelos

AU - Gao, Chuan

AU - Goel, Anuj

AU - Hagemeijer, Yanick

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KW - GENOTYPE IMPUTATION

KW - ARCHITECTURE

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

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