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

Det Juridiske Fakultet

35 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	51
Udgave nummer	4
Sider (fra-til)	636-648
Antal sider	13
ISSN	1061-4036
DOI	https://doi.org/10.1038/s41588-019-0378-y
Status	Udgivet - 1 apr. 2019

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10.1038/s41588-019-0378-y

Citationsformater

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, bind 51, nr. 4, s. 636-648. https://doi.org/10.1038/s41588-019-0378-y

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

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.",

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",

author = "Bentley, {Amy R} and Sung, {Yun J} and Brown, {Michael R} and Winkler, {Thomas W} and Kraja, {Aldi T} and Ioanna Ntalla and Karen Schwander and Chasman, {Daniel I} and Elise Lim and Xuan Deng and Xiuqing Guo and Jingmin Liu and Yingchang Lu and Ching-Yu Cheng and Xueling Sim and Dina Vojinovic and Huffman, {Jennifer E} and Musani, {Solomon K} and Changwei Li and Feitosa, {Mary F} and Richard, {Melissa A} and Raymond Noordam and Jenna Baker and Guanjie Chen and Hugues Aschard and Bartz, {Traci M} and Jingzhong Ding and Rajkumar Dorajoo and Manning, {Alisa K} and Tuomo Rankinen and Smith, {Albert V} and Tajuddin, {Salman M} and Wei Zhao and Mariaelisa Graff and Maris Alver and Mathilde Boissel and Chai, {Jin Fang} and Xu Chen and Jasmin Divers and Evangelos Evangelou and Chuan Gao and Anuj Goel and Yanick Hagemeijer and Harris, {Sarah E} and Hartwig, {Fernando P} and Zhao, {Jing Hua} and Kaare Christensen and Kilpel{\"a}inen, {Tuomas O} and Jun-Sing Wang and Loos, {Ruth J F} and {COGENT-Kidney Consortium}",

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doi = "10.1038/s41588-019-0378-y",

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T1 - Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids

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

Y1 - 2019/4/1

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

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