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)

1 ITU - IT University of Copenhagen
2 MSSM - Icahn School of Medicine at Mount Sinai [New York]
3 NIH - National Institutes of Health [Bethesda]
4 Leiden University Medical Center (LUMC)
5 Washington University School of Medicine in St. Louis
6 University of Regensburg
7 Brigham and Women's Hospital [Boston]
8 HMS - Harvard Medical School [Boston]
9 Massachusetts General Hospital [Boston]
10 QMUL - Queen Mary University of London
11 Département de Biologie Computationnelle - Department of Computational Biology
12 UTHealth - The University of Texas Health Science Center at Houston
13 WUSTL - Washington University in Saint Louis
14 Institut Pasteur de Lille
15 University of Washington [Seattle]

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.

Domains: Human genetics; Santé publique et épidémiologie; Methodology [stat.ME]; Applications [stat.AP]; Bioinformatics [q-bio.QM]

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⟩