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

Tuomas O Kilpeläinen; Amy R Bentley; Raymond Noordam; Yun Ju Sung; Karen Schwander; Thomas W Winkler; Hermina Jakupović; Daniel I Chasman; Alisa Manning; Ioanna Ntalla; Hugues Aschard; Michael R Brown; Lisa de las Fuentes; Nora Franceschini; Xiuqing Guo; Dina Vojinovic; Stella Aslibekyan; Mary F Feitosa; Minjung Kho; Solomon K Musani; Melissa Richard; Heming Wang; Zhe Wang; Traci M Bartz; Lawrence F Bielak; Archie Campbell; Rajkumar Dorajoo; Virginia Fisher; Fernando P Hartwig; Andrea R V R Horimoto; Changwei Li; Kurt K Lohman; Jonathan Marten; Xueling Sim; Albert V Smith; Salman M Tajuddin; Maris Alver; Marzyeh Amini; Mathilde Boissel; Jin Fang Chai; Xu Chen; Jasmin Divers; Evangelos Evangelou; Chuan Gao; Mariaelisa Graff; Sarah E Harris; Meian He; Fang-Chi Hsu; Anne U Jackson; Jing Hua Zhao; Aldi T Kraja; Brigitte Kühnel; Federica Laguzzi; Leo-Pekka Lyytikäinen; Ilja M Nolte; Rainer Rauramaa; Muhammad Riaz; Antonietta Robino; Rico Rueedi; Heather M Stringham; Fumihiko Takeuchi; Peter J van der Most; Tibor V Varga; Niek Verweij; Erin B Ware; Wanqing Wen; Xiaoyin Li; Lisa R Yanek; Najaf Amin; Donna K 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 S de Vries; Ayşe Demirkan; Jingzhong Ding; Charles B Eaton; Jessica D Faul; Yechiel Friedlander; Kelley P Gabriel; Mohsen Ghanbari; Franco Giulianini; Chi Charles Gu; Dongfeng Gu; Tamara B Harris; Jiang He; Sami Heikkinen; Chew-Kiat Heng; Steven C Hunt; M Arfan Ikram; Jost B Jonas; Woon-Puay Koh; Pirjo Komulainen; Jose E Krieger; Lifelines Cohort Study

doi:10.1038/s41467-018-08008-w

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

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

Tuomas O Kilpeläinen, Amy R Bentley, Raymond Noordam, Yun Ju Sung, Karen Schwander, Thomas W Winkler, Hermina Jakupović, Daniel I Chasman, Alisa Manning, Ioanna Ntalla, …

Nature communications, Vol.10(1), pp.376-11

22/01/2019

DOI: https://doi.org/10.1038/s41467-018-08008-w

PMID: 30670697

Abstract

Adolescent

Adult

Aged

Aged, 80 and over

Asian People - genetics

Black People - genetics

Brazil

Calcium-Binding Proteins - genetics

Cholesterol - blood

Cholesterol, HDL - blood

Cholesterol, HDL - genetics

Cholesterol, LDL - blood

Cholesterol, LDL - genetics

Exercise

Female

Genetic Loci - genetics

Genome-Wide Association Study

Genotype

Hispanic or Latino - genetics

Humans

LIM-Homeodomain Proteins - genetics

Lipid Metabolism - genetics

Lipids - blood

Lipids - genetics

Male

Membrane Proteins - genetics

Microtubule-Associated Proteins - genetics

Middle Aged

Muscle Proteins - genetics

Nerve Tissue Proteins - genetics

Transcription Factors - genetics

Triglycerides - blood

Triglycerides - genetics

White People - genetics

Young Adult

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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Title: Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
Creators: Tuomas O Kilpeläinen - University of Copenhagen
Amy R Bentley - National Human Genome Research Institute
Raymond Noordam - Leiden University Medical Center
Yun Ju Sung - Division of Biostatistics, Washington University School of Medicine, St. Louis, 63110, MO, USA
Karen Schwander - Washington University in St. Louis
Thomas W Winkler - University of Regensburg
Hermina Jakupović - Novo Nordisk Foundation
Daniel I Chasman - Harvard University
Alisa Manning - Massachusetts General Hospital
Ioanna Ntalla - Queen Mary University of London
Hugues Aschard - Harvard University
Michael R Brown - The University of Texas Health Science Center at Houston
Lisa de las Fuentes - Washington University in St. Louis
Nora Franceschini - University of North Carolina at Chapel Hill
Xiuqing Guo - The Lundquist Institute
Dina Vojinovic - Erasmus MC
Stella Aslibekyan - University of Alabama at Birmingham
Mary F Feitosa - Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, 63108, MO, USA
Minjung Kho - University of Michigan–Ann Arbor
Solomon K Musani - University of Mississippi Medical Center
Melissa Richard - The University of Texas Health Science Center at Houston
Heming Wang - Brigham and Women's Hospital
Zhe Wang - The University of Texas Health Science Center at Houston
Traci M Bartz - University of Washington
Lawrence F Bielak - University of Michigan–Ann Arbor
Archie Campbell - Edinburgh Cancer Research
Rajkumar Dorajoo - Agency for Science, Technology and Research
Virginia Fisher - Boston University
Fernando P Hartwig - University of Bristol
Andrea R V R Horimoto - Universidade de São Paulo
Changwei Li - University of Georgia
Kurt K Lohman - Wake Forest University
Jonathan Marten - MRC Institute of Genetics and Molecular Medicine
Xueling Sim - National University of Singapore
Albert V Smith - Icelandic Heart Association
Salman M Tajuddin - National Institute on Aging
Maris Alver - University of Tartu
Marzyeh Amini - University Medical Center Groningen
Mathilde Boissel - Institut Pasteur de Lille
Jin Fang Chai - National University Health System
Xu Chen - Karolinska Institutet
Jasmin Divers - Wake Forest University
Evangelos Evangelou - University of Ioannina
Chuan Gao - Wake Forest University
Mariaelisa Graff - University of North Carolina at Chapel Hill
Sarah E Harris - University of Edinburgh
Meian He - Huazhong University of Science and Technology
Fang-Chi Hsu - Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, 27157, NC, USA
Anne U Jackson - University of Michigan–Ann Arbor
Jing Hua Zhao - MRC Epidemiology Unit
Aldi T Kraja - Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, 63108, MO, USA
Brigitte Kühnel - Helmholtz Zentrum München
Federica Laguzzi - Karolinska Institutet
Leo-Pekka Lyytikäinen - University of Tampere
Ilja M Nolte - University Medical Center Groningen
Rainer Rauramaa - Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland
Muhammad Riaz - Infant
Antonietta Robino - IRCCS Materno Infantile Burlo Garofolo
Rico Rueedi - SIB Swiss Institute of Bioinformatics
Heather M Stringham - University of Michigan–Ann Arbor
Fumihiko Takeuchi - National Center for Global Health and Medicine
Peter J van der Most - University Medical Center Groningen
Tibor V Varga - Skåne University Hospital
Niek Verweij - University of Groningen
Erin B Ware - University of Michigan–Ann Arbor
Wanqing Wen - Vanderbilt University
Xiaoyin Li - Case Western Reserve University
Lisa R Yanek - Johns Hopkins Medicine
Najaf Amin - Erasmus MC
Donna K Arnett - University of Kentucky
Eric Boerwinkle - Baylor College of Medicine
Marco Brumat - University of Trieste
Brian Cade - Brigham and Women's Hospital
Mickaël Canouil - Université de Lille
Yii-Der Ida Chen - The Lundquist Institute
Maria Pina Concas - IRCCS Materno Infantile Burlo Garofolo
John Connell - Ninewells Hospital
Renée de Mutsert - Leiden University Medical Center
H Janaka de Silva - University of Kelaniya
Paul S de Vries - The University of Texas Health Science Center at Houston
Ayşe Demirkan - Erasmus MC
Jingzhong Ding - Wake Forest University
Charles B Eaton - Brown University
Jessica D Faul - University of Michigan–Ann Arbor
Yechiel Friedlander - Hadassah Medical Center
Kelley P Gabriel - The University of Texas Health Science Center at Houston
Mohsen Ghanbari - Mashhad University of Medical Sciences
Franco Giulianini - Brigham and Women's Hospital
Chi Charles Gu - Washington University in St. Louis
Dongfeng Gu - Chinese Academy of Medical Sciences & Peking Union Medical College
Tamara B Harris - National Institute on Aging
Jiang He - Tulane University
Sami Heikkinen - University of Eastern Finland
Chew-Kiat Heng - Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, 119228, Singapore
Steven C Hunt - Weill Cornell Medical College in Qatar
M Arfan Ikram - Erasmus MC
Jost B Jonas - University Medical Centre Mannheim
Woon-Puay Koh - Duke-NUS Medical School
Pirjo Komulainen - Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland
Jose E Krieger - Universidade de São Paulo
Lifelines Cohort Study
Publication Details: Nature communications, Vol.10(1), pp.376-11
Date published: 22/01/2019
Grant note: UM1 CA182910 / NCI NIH HHS K01 HL135405 / NHLBI NIH HHS R01 DK062370 / NIDDK NIH HHS R01 AG055406 / NIA NIH HHS MR/L01632X/1 / Medical Research Council R01 HL120393 / NHLBI NIH HHS K01 HL136700 / NHLBI NIH HHS R01 DK072193 / NIDDK NIH HHS R01 DK107786 / NIDDK NIH HHS R01 HL119443 / NHLBI NIH HHS
Identifiers: 99929060402346
Academic Unit: Institute for Sustainability; Surrey Institute for People-Centred AI; School of Biosciences
Language: English
Resource Type: Journal article

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

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