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 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; Jing Hua Zhao; Kaare Christensen; Tuomas O Kilpeläinen; Jun-Sing Wang; Ruth J F Loos; COGENT-Kidney Consortium

doi:10.1038/s41588-019-0378-y

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, Jing Hua Zhao, Kaare Christensen, Tuomas O Kilpeläinen, Jun-Sing Wang, Ruth J F Loos, COGENT-Kidney Consortium

Faculty of Law

35 Citations (Scopus)

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 language	English
Journal	Nature Genetics
Volume	51
Issue number	4
Pages (from-to)	636-648
Number of pages	13
ISSN	1061-4036
DOIs	https://doi.org/10.1038/s41588-019-0378-y
Publication status	Published - 1 Apr 2019

Keywords

Adolescent
Adult
Aged
Aged, 80 and over
Female
Genome-Wide Association Study/methods
Genotype
Humans
Life Style
Linkage Disequilibrium/genetics
Lipids/blood
Male
Middle Aged
Smoking/blood
Young Adult

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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 new 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, Zhao, JH, Christensen, K, Kilpeläinen, TO, Wang, J-S, Loos, RJF & COGENT-Kidney Consortium 2019, 'Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new 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 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.",

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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

AU - Harris, Sarah E

AU - Hartwig, Fernando P

AU - Zhao, Jing Hua

AU - Christensen, Kaare

AU - Kilpeläinen, Tuomas O

AU - Wang, Jun-Sing

AU - Loos, Ruth J F

AU - COGENT-Kidney Consortium

PY - 2019/4/1

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N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Female

KW - Genome-Wide Association Study/methods

KW - Genotype

KW - Humans

KW - Life Style

KW - Linkage Disequilibrium/genetics

KW - Lipids/blood

KW - Male

KW - Middle Aged

KW - Smoking/blood

KW - Young Adult

U2 - 10.1038/s41588-019-0378-y

DO - 10.1038/s41588-019-0378-y

M3 - Journal article

C2 - 30926973

SN - 1061-4036

VL - 51

SP - 636

EP - 648

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

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

Abstract

Keywords

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