Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Paul S de Vries; Michael R Brown; Amy R Bentley; Yun J Sung; Thomas W Winkler; Ioanna Ntalla; Karen Schwander; Aldi T Kraja; Xiuqing Guo; Nora Franceschini; Ching-Yu Cheng; Xueling Sim; Dina Vojinovic; Jennifer E Huffman; Solomon K Musani; Changwei Li; Mary F Feitosa; Melissa A Richard; Raymond Noordam; Hugues Aschard; Traci M Bartz; Lawrence F Bielak; Xuan Deng; Rajkumar Dorajoo; Kurt K Lohman; Alisa K Manning; Tuomo Rankinen; Albert V Smith; Salman M Tajuddin; Evangelos Evangelou; Mariaelisa Graff; Maris Alver; Mathilde Boissel; Jin Fang Chai; Xu Chen; Jasmin Divers; Ilaria Gandin; Chuan Gao; Anuj Goel; Yanick Hagemeijer; Sarah E Harris; Fernando P Hartwig; Meian He; Andrea R V R Horimoto; Fang-Chi Hsu; Anne U Jackson; Anuradhani Kasturiratne; Pirjo Komulainen; Jing Hua Zhao; Tuomas O Kilpeläinen; InterAct Consortium

doi:10.1093/aje/kwz005

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Paul S de Vries, Michael R Brown, Amy R Bentley, Yun J Sung, Thomas W Winkler, Ioanna Ntalla, Karen Schwander, Aldi T Kraja, Xiuqing Guo, Nora Franceschini, Ching-Yu Cheng, Xueling Sim, Dina Vojinovic, Jennifer E Huffman, Solomon K Musani, Changwei Li, Mary F Feitosa, Melissa A Richard, Raymond Noordam, Hugues AschardTraci M Bartz, Lawrence F Bielak, Xuan Deng, Rajkumar Dorajoo, Kurt K Lohman, Alisa K Manning, Tuomo Rankinen, Albert V Smith, Salman M Tajuddin, Evangelos Evangelou, Mariaelisa Graff, Maris Alver, Mathilde Boissel, Jin Fang Chai, Xu Chen, Jasmin Divers, Ilaria Gandin, Chuan Gao, Anuj Goel, Yanick Hagemeijer, Sarah E Harris, Fernando P Hartwig, Meian He, Andrea R V R Horimoto, Fang-Chi Hsu, Anne U Jackson, Anuradhani Kasturiratne, Pirjo Komulainen, Jing Hua Zhao, Tuomas O Kilpeläinen, InterAct Consortium

27 Citationer (Scopus)

Abstract

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-Alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2- degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10?6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10?8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

Originalsprog	Engelsk
Tidsskrift	American Journal of Epidemiology
Vol/bind	188
Udgave nummer	6
Sider (fra-til)	1033-1054
ISSN	0002-9262
DOI	https://doi.org/10.1093/aje/kwz005
Status	Udgivet - 1 jun. 2019

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10.1093/aje/kwz005

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de Vries, P. S., Brown, M. R., Bentley, A. R., Sung, Y. J., Winkler, T. W., Ntalla, I., Schwander, K., Kraja, A. T., Guo, X., Franceschini, N., Cheng, C.-Y., Sim, X., Vojinovic, D., Huffman, J. E., Musani, S. K., Li, C., Feitosa, M. F., Richard, M. A., Noordam, R., ... InterAct Consortium (2019). Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions. American Journal of Epidemiology, 188(6), 1033-1054. https://doi.org/10.1093/aje/kwz005

de Vries, PS, Brown, MR, Bentley, AR, Sung, YJ, Winkler, TW, Ntalla, I, Schwander, K, Kraja, AT, Guo, X, Franceschini, N, Cheng, C-Y, Sim, X, Vojinovic, D, Huffman, JE, Musani, SK, Li, C, Feitosa, MF, Richard, MA, Noordam, R, Aschard, H, Bartz, TM, Bielak, LF, Deng, X, Dorajoo, R, Lohman, KK, Manning, AK, Rankinen, T, Smith, AV, Tajuddin, SM, Evangelou, E, Graff, M, Alver, M, Boissel, M, Chai, JF, Chen, X, Divers, J, Gandin, I, Gao, C, Goel, A, Hagemeijer, Y, Harris, SE, Hartwig, FP, He, M, Horimoto, ARVR, Hsu, F-C, Jackson, AU, Kasturiratne, A, Komulainen, P, Zhao, JH, Kilpeläinen, TO & InterAct Consortium 2019, 'Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions', American Journal of Epidemiology, bind 188, nr. 6, s. 1033-1054. https://doi.org/10.1093/aje/kwz005

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title = "Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions",

abstract = "A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-Alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2- degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10?6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10?8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.",

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T1 - Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

AU - de Vries, Paul S

AU - Brown, Michael R

AU - Bentley, Amy R

AU - Sung, Yun J

AU - Winkler, Thomas W

AU - Ntalla, Ioanna

AU - Schwander, Karen

AU - Kraja, Aldi T

AU - Guo, Xiuqing

AU - Franceschini, Nora

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 - Aschard, Hugues

AU - Bartz, Traci M

AU - Bielak, Lawrence F

AU - Deng, Xuan

AU - Dorajoo, Rajkumar

AU - Lohman, Kurt K

AU - Manning, Alisa K

AU - Rankinen, Tuomo

AU - Smith, Albert V

AU - Tajuddin, Salman M

AU - Evangelou, Evangelos

AU - Graff, Mariaelisa

AU - Alver, Maris

AU - Boissel, Mathilde

AU - Chai, Jin Fang

AU - Chen, Xu

AU - Divers, Jasmin

AU - Gandin, Ilaria

AU - Gao, Chuan

AU - Goel, Anuj

AU - Hagemeijer, Yanick

AU - Harris, Sarah E

AU - Hartwig, Fernando P

AU - He, Meian

AU - Horimoto, Andrea R V R

AU - Hsu, Fang-Chi

AU - Jackson, Anne U

AU - Kasturiratne, Anuradhani

AU - Komulainen, Pirjo

AU - Zhao, Jing Hua

AU - Kilpeläinen, Tuomas O

AU - InterAct Consortium

PY - 2019/6/1

Y1 - 2019/6/1

N2 - A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-Alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2- degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10?6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10?8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

AB - A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-Alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2- degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10?6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10?8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

U2 - 10.1093/aje/kwz005

DO - 10.1093/aje/kwz005

M3 - Journal article

C2 - 30698716

SN - 0002-9262

VL - 188

SP - 1033

EP - 1054

JO - American Journal of Epidemiology

JF - American Journal of Epidemiology

IS - 6

ER -

Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Abstract

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