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Journal Articles Nature Communications Year : 2019

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Tuomas Kilpeläinen (1, 2) , Amy Bentley (3) , Raymond Noordam (4) , Yun Ju Sung (5) , Karen Schwander (5) , Thomas Winkler (6) , Hermina Jakupović (1) , Daniel Chasman (7, 8) , Alisa Manning (9, 8) , Ioanna Ntalla (10) , Hugues Aschard (8, 11) , Michael Brown (12) , Lisa de Las Fuentes (13) , Nora Franceschini , Xiuqing Guo , Dina Vojinovic , Stella Aslibekyan , Mary Feitosa , Minjung Kho , Solomon Musani , Melissa Richard , Heming Wang , Zhe Wang , Traci Bartz , Lawrence Bielak , Archie Campbell , Rajkumar Dorajoo , Virginia Fisher , Fernando Hartwig , Andrea Horimoto , Changwei Li , Kurt Lohman , Jonathan Marten , Xueling Sim , Albert Smith , Salman Tajuddin , Maris Alver , Marzyeh Amini , Mathilde Boissel (14) , Jin Fang Chai , Xu Chen , Jasmin Divers , Evangelos Evangelou , Chuan Gao , Mariaelisa Graff , Sarah Harris , Meian He , Fang-Chi Hsu , Anne Jackson , Jing Hua Zhao , Aldi Kraja , Brigitte Kühnel , Federica Laguzzi , Leo-Pekka Lyytikäinen , Ilja Nolte , Rainer Rauramaa , Muhammad Riaz , Antonietta Robino , Rico Rueedi , Heather Stringham , Fumihiko Takeuchi , Peter van Der Most , Tibor Varga , Niek Verweij , Erin Ware , Wanqing Wen , Xiaoyin Li , Lisa Yanek , Najaf Amin , Donna Arnett , Eric Boerwinkle , Marco Brumat , Brian Cade , Mickaël Canouil , Yii-Der Ida Chen , Maria Pina Concas , John Connell , Renée de Mutsert , H Janaka de Silva , Paul de Vries , Ayşe Demirkan , Jingzhong Ding , Charles Eaton , Jessica Faul , Yechiel Friedlander , Kelley Gabriel , Mohsen Ghanbari , Franco Giulianini , Chi Charles Gu , Dongfeng Gu , Tamara Harris , Jiang He , Sami Heikkinen , Chew-Kiat Heng , Steven Hunt , M Arfan Ikram , Jost Jonas , Woon-Puay Koh , Pirjo Komulainen , Jose Krieger , Stephen Kritchevsky , Zoltán Kutalik , Johanna Kuusisto , Carl Langefeld , Claudia Langenberg , Lenore Launer , Karin Leander , Rozenn Lemaitre , Cora Lewis , Jingjing Liang , Jianjun Liu , Reedik Mägi , Ani Manichaikul , Thomas Meitinger , Andres Metspalu , Yuri Milaneschi , Karen Mohlke , Thomas Mosley , Alison Murray , Mike Nalls , Ei-Ei Khaing Nang , Christopher Nelson , Sotoodehnia Nona , Jill Norris , Chiamaka Vivian Nwuba , Jeff O'Connell , Nicholette Palmer , George Papanicolau , Raha Pazoki , Nancy Pedersen , Annette Peters , Patricia Peyser , Ozren Polasek , David Porteous , Alaitz Poveda , Olli Raitakari , Stephen Rich , Neil Risch , Jennifer Robinson , Lynda Rose , Igor Rudan , Pamela Schreiner , Robert Scott , Stephen Sidney , Mario Sims , Jennifer Smith , Harold Snieder , Tamar Sofer , John Starr , Barbara Sternfeld , Konstantin Strauch , Hua Tang , Kent Taylor , Michael Tsai , Jaakko Tuomilehto , André Uitterlinden , M Yldau van Der Ende , Diana van Heemst , Trudy Voortman , Melanie Waldenberger , Patrik Wennberg , Gregory Wilson , Yong-Bing Xiang , Jie Yao , Caizheng Yu , Jian-Min Yuan , Wei Zhao , Alan Zonderman , Diane Becker , Michael Boehnke , Donald Bowden , Ulf de Faire , Ian Deary , Paul Elliott , Tõnu Esko , Barry Freedman , Philippe Froguel , Paolo Gasparini , Christian Gieger , Norihiro Kato , Markku Laakso , Timo Lakka , Terho Lehtimäki , Patrik Magnusson , Albertine Oldehinkel , Brenda Penninx , Nilesh Samani , Xiao-Ou Shu , Pim van Der Harst , Jana van Vliet-Ostaptchouk , Peter Vollenweider , Lynne Wagenknecht , Ya Wang , Nicholas Wareham , David Weir , Tangchun Wu , Wei Zheng , Xiaofeng Zhu , Michele Evans , Paul Franks , Vilmundur Gudnason , Caroline Hayward , Bernardo Horta , Tanika Kelly , Yongmei Liu , Kari North , Alexandre Pereira , Paul Ridker , E Shyong Tai , Rob van Dam , Ervin Fox , Sharon Kardia , Ching-Ti Liu , Dennis Mook-Kanamori , Michael Province , Susan Redline , Cornelia van Duijn , Jerome Rotter , Charles Kooperberg , W James Gauderman , Bruce Psaty , Kenneth Rice (15) , Patricia Munroe (10) , Myriam Fornage (12) , L Adrienne Cupples , Charles Rotimi (3) , Alanna Morrison (12) , Dabeeru Rao (5) , Ruth Loos (2)
Nora Franceschini
  • Function : Author
Xiuqing Guo
  • Function : Author
Dina Vojinovic
  • Function : Author
Stella Aslibekyan
  • Function : Author
Mary Feitosa
  • Function : Author
Minjung Kho
  • Function : Author
Solomon Musani
  • Function : Author
Melissa Richard
  • Function : Author
Heming Wang
  • Function : Author
Zhe Wang
  • Function : Author
Traci Bartz
  • Function : Author
Lawrence Bielak
  • Function : Author
Archie Campbell
  • Function : Author
Rajkumar Dorajoo
Virginia Fisher
  • Function : Author
Fernando Hartwig
  • Function : Author
Andrea Horimoto
  • Function : Author
Changwei Li
  • Function : Author
Kurt Lohman
  • Function : Author
Jonathan Marten
  • Function : Author
Xueling Sim
  • Function : Author
Albert Smith
  • Function : Author
Salman Tajuddin
  • Function : Author
Maris Alver
  • Function : Author
Marzyeh Amini
  • Function : Author
Jin Fang Chai
  • Function : Author
Xu Chen
  • Function : Author
Jasmin Divers
  • Function : Author
Evangelos Evangelou
  • Function : Author
Chuan Gao
  • Function : Author
Mariaelisa Graff
  • Function : Author
Sarah Harris
Meian He
  • Function : Author
Fang-Chi Hsu
  • Function : Author
Anne Jackson
  • Function : Author
Jing Hua Zhao
  • Function : Author
Aldi Kraja
  • Function : Author
Brigitte Kühnel
  • Function : Author
Federica Laguzzi
  • Function : Author
Leo-Pekka Lyytikäinen
  • Function : Author
Ilja Nolte
  • Function : Author
Rainer Rauramaa
  • Function : Author
Muhammad Riaz
  • Function : Author
Antonietta Robino
  • Function : Author
Rico Rueedi
  • Function : Author
Heather Stringham
  • Function : Author
Fumihiko Takeuchi
  • Function : Author
Peter van Der Most
  • Function : Author
Tibor Varga
Niek Verweij
  • Function : Author
Erin Ware
  • Function : Author
Wanqing Wen
  • Function : Author
Xiaoyin Li
  • Function : Author
Lisa Yanek
  • Function : Author
Najaf Amin
  • Function : Author
Donna Arnett
  • Function : Author
Eric Boerwinkle
  • Function : Author
Marco Brumat
  • Function : Author
Brian Cade
  • Function : Author
Mickaël Canouil
Yii-Der Ida Chen
  • Function : Author
Maria Pina Concas
  • Function : Author
John Connell
  • Function : Author
Renée de Mutsert
  • Function : Author
H Janaka de Silva
  • Function : Author
Paul de Vries
  • Function : Author
Ayşe Demirkan
  • Function : Author
Jingzhong Ding
  • Function : Author
Charles Eaton
  • Function : Author
Jessica Faul
  • Function : Author
Yechiel Friedlander
  • Function : Author
Kelley Gabriel
  • Function : Author
Mohsen Ghanbari
  • Function : Author
Franco Giulianini
  • Function : Author
Chi Charles Gu
  • Function : Author
Dongfeng Gu
  • Function : Author
Tamara Harris
  • Function : Author
Jiang He
  • Function : Author
Sami Heikkinen
  • Function : Author
Chew-Kiat Heng
  • Function : Author
Steven Hunt
  • Function : Author
M Arfan Ikram
  • Function : Author
Jost Jonas
  • Function : Author
Woon-Puay Koh
  • Function : Author
Pirjo Komulainen
  • Function : Author
Jose Krieger
  • Function : Author
Stephen Kritchevsky
  • Function : Author
Zoltán Kutalik
  • Function : Author
Johanna Kuusisto
  • Function : Author
Carl Langefeld
  • Function : Author
Claudia Langenberg
  • Function : Author
Lenore Launer
  • Function : Author
Karin Leander
Rozenn Lemaitre
  • Function : Author
Cora Lewis
  • Function : Author
Jingjing Liang
Jianjun Liu
Reedik Mägi
  • Function : Author
Ani Manichaikul
  • Function : Author
Thomas Meitinger
  • Function : Author
Andres Metspalu
  • Function : Author
Yuri Milaneschi
  • Function : Author
Karen Mohlke
  • Function : Author
Thomas Mosley
  • Function : Author
Alison Murray
Mike Nalls
  • Function : Author
Ei-Ei Khaing Nang
  • Function : Author
Christopher Nelson
  • Function : Author
Sotoodehnia Nona
  • Function : Author
Jill Norris
  • Function : Author
Chiamaka Vivian Nwuba
  • Function : Author
Jeff O'Connell
  • Function : Author
Nicholette Palmer
  • Function : Author
George Papanicolau
  • Function : Author
Raha Pazoki
  • Function : Author
Nancy Pedersen
  • Function : Author
Annette Peters
Patricia Peyser
  • Function : Author
Ozren Polasek
  • Function : Author
David Porteous
  • Function : Author
Alaitz Poveda
  • Function : Author
Olli Raitakari
  • Function : Author
Stephen Rich
  • Function : Author
Neil Risch
  • Function : Author
Jennifer Robinson
  • Function : Author
Lynda Rose
  • Function : Author
Igor Rudan
  • Function : Author
Pamela Schreiner
  • Function : Author
Robert Scott
  • Function : Author
Stephen Sidney
  • Function : Author
Mario Sims
  • Function : Author
Jennifer Smith
  • Function : Author
Harold Snieder
  • Function : Author
Tamar Sofer
  • Function : Author
John Starr
  • Function : Author
Barbara Sternfeld
  • Function : Author
Konstantin Strauch
  • Function : Author
Hua Tang
  • Function : Author
Kent Taylor
  • Function : Author
Michael Tsai
  • Function : Author
Jaakko Tuomilehto
  • Function : Author
André Uitterlinden
  • Function : Author
M Yldau van Der Ende
  • Function : Author
Diana van Heemst
  • Function : Author
Trudy Voortman
Melanie Waldenberger
  • Function : Author
Patrik Wennberg
  • Function : Author
Gregory Wilson
  • Function : Author
Yong-Bing Xiang
  • Function : Author
Jie Yao
  • Function : Author
Caizheng Yu
  • Function : Author
Jian-Min Yuan
  • Function : Author
Wei Zhao
  • Function : Author
Alan Zonderman
  • Function : Author
Diane Becker
  • Function : Author
Michael Boehnke
  • Function : Author
Donald Bowden
  • Function : Author
Ulf de Faire
  • Function : Author
Ian Deary
  • Function : Author
Paul Elliott
Tõnu Esko
  • Function : Author
Barry Freedman
  • Function : Author
Philippe Froguel
  • Function : Author
Paolo Gasparini
  • Function : Author
Christian Gieger
  • Function : Author
Norihiro Kato
  • Function : Author
Markku Laakso
  • Function : Author
Timo Lakka
  • Function : Author
Terho Lehtimäki
  • Function : Author
Patrik Magnusson
  • Function : Author
Albertine Oldehinkel
  • Function : Author
Brenda Penninx
  • Function : Author
Nilesh Samani
Xiao-Ou Shu
  • Function : Author
Pim van Der Harst
  • Function : Author
Jana van Vliet-Ostaptchouk
  • Function : Author
Peter Vollenweider
  • Function : Author
Lynne Wagenknecht
  • Function : Author
Ya Wang
  • Function : Author
Nicholas Wareham
  • Function : Author
David Weir
  • Function : Author
Tangchun Wu
  • Function : Author
Wei Zheng
Xiaofeng Zhu
  • Function : Author
Michele Evans
  • Function : Author
Paul Franks
  • Function : Author
Vilmundur Gudnason
  • Function : Author
Caroline Hayward
  • Function : Author
Bernardo Horta
  • Function : Author
Tanika Kelly
  • Function : Author
Yongmei Liu
  • Function : Author
Kari North
  • Function : Author
Alexandre Pereira
Paul Ridker
  • Function : Author
E Shyong Tai
  • Function : Author
Rob van Dam
  • Function : Author
Ervin Fox
  • Function : Author
Sharon Kardia
  • Function : Author
Ching-Ti Liu
  • Function : Author
Dennis Mook-Kanamori
  • Function : Author
Michael Province
  • Function : Author
Susan Redline
  • Function : Author
Cornelia van Duijn
  • Function : Author
Jerome Rotter
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Charles Kooperberg
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W James Gauderman
  • Function : Author
Bruce Psaty
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L Adrienne Cupples
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Abstract

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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Dates and versions

pasteur-03278556 , version 1 (05-07-2021)

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Tuomas Kilpeläinen, Amy Bentley, Raymond Noordam, Yun Ju Sung, Karen Schwander, et al.. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity. Nature Communications, 2019, 10 (1), pp.376. ⟨10.1038/s41467-018-08008-w⟩. ⟨pasteur-03278556⟩

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