Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions - Institut Pasteur Access content directly
Journal Articles American Journal of Epidemiology Year : 2019

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

Paul de Vries (1) , Michael Brown (1) , Amy Bentley (2) , Yun Sung (1, 3) , Thomas Winkler (4) , Ioanna Ntalla (5) , Karen Schwander (6) , Aldi Kraja (3) , Xiuqing Guo (7) , Nora Franceschini (8) , Ching-Yu Cheng (9, 10) , Xueling Sim (10) , Dina Vojinovic (11) , Jennifer Huffman , Solomon Musani , Changwei Li , Mary Feitosa (3) , Melissa Richard , Raymond Noordam , Hugues Aschard (12) , Traci Bartz , Lawrence Bielak , Xuan Deng , Rajkumar Dorajoo , Kurt Lohman , Alisa Manning , Tuomo Rankinen , Albert Smith , Salman Tajuddin , Evangelos Evangelou , Mariaelisa Graff (8) , Maris Alver , Mathilde Boissel (13) , Jin Fang Chai (10) , Xu Chen , Jasmin Divers , Ilaria Gandin , Chuan Gao , Anuj Goel , Yanick Hagemeijer , Sarah Harris , Fernando Hartwig , Meian He , Andrea Horimoto , Fang-Chi Hsu , Anne Jackson , Anuradhani Kasturiratne , Pirjo Komulainen , Brigitte Kühnel , Federica Laguzzi , Joseph Lee , Jian'An Luan , Leo-Pekka Lyytikäinen , Nana Matoba , Ilja Nolte , Maik Pietzner , Muhammad Riaz , M Abdullah Said , Robert Scott , Tamar Sofer , Alena Stančáková , Fumihiko Takeuchi , Bamidele Tayo , Peter van Der Most , Tibor Varga , Yajuan Wang (8) , Erin Ware , Wanqing Wen , Lisa Yanek , Weihua Zhang , Jing Hua Zhao , Saima Afaq , Najaf Amin (11) , Marzyeh Amini , Dan Arking , Tin Aung (9) , Christie Ballantyne , Eric Boerwinkle , Ulrich Broeckel , Archie Campbell , Mickaël Canouil (13) , Sabanayagam Charumathi (9) , Yii-Der Ida Chen (7) , John Connell , Ulf de Faire , Lisa de Las Fuentes (3) , Renée de Mutsert , H Janaka de Silva , Jingzhong Ding , Anna Dominiczak , Qing Duan , Charles Eaton , Ruben Eppinga , Jessica Faul , Virginia Fisher , Terrence Forrester , Oscar Franco (11) , Yechiel Friedlander , Mohsen Ghanbari (11) , Franco Giulianini , Hans Grabe , Megan Grove (1) , C Charles Gu (3) , Tamara Harris , Sami Heikkinen , Chew-Kiat Heng , Makoto Hirata , James Hixson , Barbara Howard , M Arfan Ikram (11) , David Jacobs , Craig Johnson , Jost Bruno Jonas , Candace Kammerer , Tomohiro Katsuya , Chiea Chuen Khor , Tuomas Kilpeläinen , Woon-Puay Koh (10) , Heikki Koistinen , Ivana Kolcic , Charles Kooperberg , Jose Krieger , Steve Kritchevsky , Michiaki Kubo , Johanna Kuusisto , Timo Lakka , Carl Langefeld , Claudia Langenberg , Lenore Launer , Benjamin Lehne , Rozenn Lemaitre , Yize Li (3) , Jingjing Liang , Jianjun Liu , Kiang Liu , Marie Loh , Tin Louie , Reedik Mägi , Ani Manichaikul , Colin Mckenzie , Thomas Meitinger , Andres Metspalu , Yuri Milaneschi , Lili Milani , Karen Mohlke , Thomas Mosley , Kenneth Mukamal , Mike Nalls , Matthias Nauck , Christopher Nelson , Nona Sotoodehnia , Jeff O'Connell , Nicholette Palmer , Raha Pazoki , Nancy Pedersen , Annette Peters , Patricia Peyser , Ozren Polasek , Neil Poulter , Leslie Raffel , Olli Raitakari , Alex Reiner , Treva Rice (3) , Stephen Rich , Antonietta Robino , Jennifer Robinson , Lynda Rose , Igor Rudan , Carsten Schmidt , Pamela Schreiner , William Scott , Peter Sever , Yuan Shi (9) , Stephen Sidney , Mario Sims , Blair Smith , Jennifer Smith , Harold Snieder , John Starr , Konstantin Strauch , Nicholas Tan (9) , Kent Taylor (7) , Yik Ying Teo (10) , Yih Chung Tham (9) , André Uitterlinden (11) , Diana van Heemst , Dragana Vuckovic , Melanie Waldenberger , Lihua Wang (3) , Yujie Wang , Zhe Wang (1) , Wen Bin Wei , Christine Williams (3) , Gregory Wilson , Mary Wojczynski (3) , Jie Yao (7) , Bing Yu , Caizheng Yu , Jian-Min Yuan , Wei Zhao , Alan Zonderman , Diane Becker , Michael Boehnke , Donald Bowden , John Chambers , Ian Deary , Tõnu Esko , Martin Farrall , Paul Franks , Barry Freedman , Philippe Froguel (13) , Paolo Gasparini , Christian Gieger , Bernardo Horta , Yoichiro Kamatani , Norihiro Kato , Jaspal Kooner , Markku Laakso , Karin Leander , Terho Lehtimäki , Patrik Magnusson , Brenda Penninx , Alexandre Pereira , Rainer Rauramaa , Nilesh Samani , James Scott , Xiao-Ou Shu , Pim van Der Harst , Lynne Wagenknecht , Ya Xing Wang , Nicholas Wareham , Hugh Watkins , David Weir , Ananda Wickremasinghe , Wei Zheng , Paul Elliott , Kari North (8) , Claude Bouchard , Michele Evans , Vilmundur Gudnason , Ching-Ti Liu , Yongmei Liu , Bruce Psaty , Paul Ridker , Rob van Dam (10) , Sharon Kardia , Xiaofeng Zhu , Charles Rotimi (2) , Dennis Mook-Kanamori , Myriam Fornage (1) , Tanika Kelly , Ervin Fox , Caroline Hayward , Cornelia van Duijn (11) , E Shyong Tai (10) , Tien Yin Wong (9) , Jingmin Liu , Jerome Rotter (7) , W James Gauderman , Michael Province (3) , Patricia Munroe (5) , Kenneth Rice , Daniel Chasman , L Adrienne Cupples , Dabeeru Rao (3) , Alanna Morrison (1)
Jennifer Huffman
  • Function : Author
Solomon Musani
  • Function : Author
Changwei Li
  • Function : Author
Melissa Richard
  • Function : Author
Raymond Noordam
  • Function : Author
Traci Bartz
  • Function : Author
Lawrence Bielak
  • Function : Author
Xuan Deng
  • Function : Author
Rajkumar Dorajoo
Kurt Lohman
  • Function : Author
Alisa Manning
  • Function : Author
Tuomo Rankinen
  • Function : Author
Albert Smith
  • Function : Author
Salman Tajuddin
  • Function : Author
Evangelos Evangelou
  • Function : Author
Maris Alver
  • Function : Author
Xu Chen
  • Function : Author
Jasmin Divers
  • Function : Author
Ilaria Gandin
  • Function : Author
Chuan Gao
  • Function : Author
Anuj Goel
  • Function : Author
Yanick Hagemeijer
  • Function : Author
Sarah Harris
Fernando Hartwig
  • Function : Author
Meian He
  • Function : Author
Andrea Horimoto
  • Function : Author
Fang-Chi Hsu
  • Function : Author
Anne Jackson
  • Function : Author
Anuradhani Kasturiratne
  • Function : Author
Pirjo Komulainen
  • Function : Author
Brigitte Kühnel
  • Function : Author
Federica Laguzzi
  • Function : Author
Joseph Lee
  • Function : Author
Jian'An Luan
  • Function : Author
Leo-Pekka Lyytikäinen
  • Function : Author
Nana Matoba
  • Function : Author
Ilja Nolte
  • Function : Author
Maik Pietzner
  • Function : Author
Muhammad Riaz
  • Function : Author
M Abdullah Said
  • Function : Author
Robert Scott
  • Function : Author
Tamar Sofer
  • Function : Author
Alena Stančáková
  • Function : Author
Fumihiko Takeuchi
  • Function : Author
Bamidele Tayo
  • Function : Author
Peter van Der Most
  • Function : Author
Tibor Varga
Erin Ware
  • Function : Author
Wanqing Wen
  • Function : Author
Lisa Yanek
  • Function : Author
Weihua Zhang
  • Function : Author
Jing Hua Zhao
  • Function : Author
Saima Afaq
  • Function : Author
Marzyeh Amini
  • Function : Author
Dan Arking
  • Function : Author
Christie Ballantyne
  • Function : Author
Eric Boerwinkle
  • Function : Author
Ulrich Broeckel
  • Function : Author
Archie Campbell
  • Function : Author
Mickaël Canouil
John Connell
  • Function : Author
Ulf de Faire
  • Function : Author
Renée de Mutsert
  • Function : Author
H Janaka de Silva
  • Function : Author
Jingzhong Ding
  • Function : Author
Anna Dominiczak
  • Function : Author
Qing Duan
  • Function : Author
Charles Eaton
  • Function : Author
Ruben Eppinga
  • Function : Author
Jessica Faul
  • Function : Author
Virginia Fisher
  • Function : Author
Terrence Forrester
  • Function : Author
Yechiel Friedlander
  • Function : Author
Franco Giulianini
  • Function : Author
Hans Grabe
  • Function : Author
Tamara Harris
  • Function : Author
Sami Heikkinen
  • Function : Author
Chew-Kiat Heng
  • Function : Author
Makoto Hirata
  • Function : Author
James Hixson
  • Function : Author
Barbara Howard
  • Function : Author
David Jacobs
  • Function : Author
Craig Johnson
  • Function : Author
Jost Bruno Jonas
  • Function : Author
Candace Kammerer
  • Function : Author
Tomohiro Katsuya
  • Function : Author
Chiea Chuen Khor
Tuomas Kilpeläinen
  • Function : Author
Heikki Koistinen
  • Function : Author
Ivana Kolcic
  • Function : Author
Charles Kooperberg
  • Function : Author
Jose Krieger
  • Function : Author
Steve Kritchevsky
  • Function : Author
Michiaki Kubo
  • Function : Author
Johanna Kuusisto
  • Function : Author
Timo Lakka
  • Function : Author
Carl Langefeld
  • Function : Author
Claudia Langenberg
  • Function : Author
Lenore Launer
  • Function : Author
Benjamin Lehne
  • Function : Author
Rozenn Lemaitre
  • Function : Author
Jingjing Liang
Jianjun Liu
Kiang Liu
  • Function : Author
Marie Loh
  • Function : Author
Tin Louie
  • Function : Author
Reedik Mägi
  • Function : Author
Ani Manichaikul
  • Function : Author
Colin Mckenzie
  • Function : Author
Thomas Meitinger
  • Function : Author
Andres Metspalu
  • Function : Author
Yuri Milaneschi
  • Function : Author
Lili Milani
  • Function : Author
Karen Mohlke
  • Function : Author
Thomas Mosley
  • Function : Author
Kenneth Mukamal
  • Function : Author
Mike Nalls
  • Function : Author
Matthias Nauck
  • Function : Author
Christopher Nelson
  • Function : Author
Nona Sotoodehnia
  • Function : Author
Jeff O'Connell
  • Function : Author
Nicholette Palmer
  • Function : Author
Raha Pazoki
  • Function : Author
Nancy Pedersen
  • Function : Author
Annette Peters
Patricia Peyser
  • Function : Author
Ozren Polasek
  • Function : Author
Neil Poulter
  • Function : Author
Leslie Raffel
  • Function : Author
Olli Raitakari
  • Function : Author
Alex Reiner
  • Function : Author
Stephen Rich
  • Function : Author
Antonietta Robino
  • Function : Author
Jennifer Robinson
  • Function : Author
Lynda Rose
  • Function : Author
Igor Rudan
  • Function : Author
Carsten Schmidt
  • Function : Author
Pamela Schreiner
  • Function : Author
William Scott
  • Function : Author
Peter Sever
Stephen Sidney
  • Function : Author
Mario Sims
  • Function : Author
Blair Smith
  • Function : Author
Jennifer Smith
  • Function : Author
Harold Snieder
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John Starr
  • Function : Author
Konstantin Strauch
  • Function : Author
Diana van Heemst
  • Function : Author
Dragana Vuckovic
  • Function : Author
Melanie Waldenberger
  • Function : Author
Yujie Wang
  • Function : Author
Wen Bin Wei
  • Function : Author
Gregory Wilson
  • Function : Author
Bing Yu
Caizheng Yu
  • Function : Author
Jian-Min Yuan
  • Function : Author
Wei Zhao
  • Function : Author
Alan Zonderman
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Diane Becker
  • Function : Author
Michael Boehnke
  • Function : Author
Donald Bowden
  • Function : Author
John Chambers
  • Function : Author
Ian Deary
  • Function : Author
Tõnu Esko
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Martin Farrall
  • Function : Author
Paul Franks
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Barry Freedman
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Paolo Gasparini
  • Function : Author
Christian Gieger
  • Function : Author
Bernardo Horta
  • Function : Author
Yoichiro Kamatani
  • Function : Author
Norihiro Kato
  • Function : Author
Jaspal Kooner
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Markku Laakso
  • Function : Author
Karin Leander
Terho Lehtimäki
  • Function : Author
Patrik Magnusson
  • Function : Author
Brenda Penninx
  • Function : Author
Alexandre Pereira
Rainer Rauramaa
  • Function : Author
Nilesh Samani
James Scott
Xiao-Ou Shu
  • Function : Author
Pim van Der Harst
  • Function : Author
Lynne Wagenknecht
  • Function : Author
Ya Xing Wang
  • Function : Author
Nicholas Wareham
  • Function : Author
Hugh Watkins
  • Function : Author
David Weir
  • Function : Author
Ananda Wickremasinghe
  • Function : Author
Wei Zheng
Paul Elliott
Claude Bouchard
  • Function : Author
Michele Evans
  • Function : Author
Vilmundur Gudnason
  • Function : Author
Ching-Ti Liu
  • Function : Author
Yongmei Liu
  • Function : Author
Bruce Psaty
  • Function : Author
Paul Ridker
  • Function : Author
Sharon Kardia
  • Function : Author
Xiaofeng Zhu
  • Function : Author
Dennis Mook-Kanamori
  • Function : Author
Tanika Kelly
  • Function : Author
Ervin Fox
  • Function : Author
Caroline Hayward
  • Function : Author
Jingmin Liu
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W James Gauderman
  • Function : Author
Kenneth Rice
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Daniel Chasman
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L Adrienne Cupples
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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.

Dates and versions

pasteur-03278557 , version 1 (05-07-2021)

Identifiers

Cite

Paul de Vries, Michael Brown, Amy Bentley, Yun Sung, Thomas Winkler, et al.. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions. American Journal of Epidemiology, 2019, 188 (6), pp.1033-1054. ⟨10.1093/aje/kwz005⟩. ⟨pasteur-03278557⟩

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