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

LifeLines Cohort Study; 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; John Connell; Jennifer A. Smith; Dabeeru C. Rao; Ruth J. F. Loos

doi:10.1038/s41467-018-08008-w

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

LifeLines Cohort Study, Tuomas O. Kilpeläinen (Lead / Corresponding author), 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 KhoSolomon 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, John Connell, Jennifer A. Smith, Dabeeru C. Rao (Lead / Corresponding author), Ruth J. F. Loos (Lead / Corresponding author)

Molecular and Clinical Medicine

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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.

Original language	English
Article number	376
Pages (from-to)	1-11
Number of pages	11
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-08008-w
Publication status	Published - 22 Jan 2019

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Final published versionFinal published version, 1.71 MBLicence: CC BY

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LifeLines Cohort Study, Kilpeläinen, T. O., Bentley, A. R., Noordam, R., Sung, Y. J., Schwander, K., Winkler, T. W., Jakupović, H., Chasman, D. I., Manning, A., Ntalla, I., Aschard, H., Brown, M. R., de Las Fuentes, L., Franceschini, N., Guo, X., Vojinovic, D., Aslibekyan, S., Feitosa, M. F., ... Loos, R. J. F. (2019). Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity. Nature Communications, 10(1), 1-11. [376]. https://doi.org/10.1038/s41467-018-08008-w

@article{1c94d76bcac849b99038527084ebf58d,

title = "Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity",

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.",

author = "{LifeLines Cohort Study} and Kilpel{\"a}inen, {Tuomas O.} and Bentley, {Amy R.} and Raymond Noordam and Sung, {Yun Ju} and Karen Schwander and Winkler, {Thomas W.} and Hermina Jakupovi{\'c} and Chasman, {Daniel I.} and Alisa Manning and Ioanna Ntalla and Hugues Aschard and Brown, {Michael R.} and {de Las Fuentes}, Lisa and Nora Franceschini and Xiuqing Guo and Dina Vojinovic and Stella Aslibekyan and Feitosa, {Mary F.} and Minjung Kho and Musani, {Solomon K.} and Melissa Richard and Heming Wang and Zhe Wang and Bartz, {Traci M.} and Bielak, {Lawrence F.} and Archie Campbell and Rajkumar Dorajoo and Virginia Fisher and Hartwig, {Fernando P.} and Horimoto, {Andrea R. V. R.} and Changwei Li and Lohman, {Kurt K.} and Jonathan Marten and Xueling Sim and Smith, {Albert V.} and Tajuddin, {Salman M.} and Maris Alver and Marzyeh Amini and Mathilde Boissel and Chai, {Jin Fang} and Xu Chen and Jasmin Divers and Evangelos Evangelou and Chuan Gao and Mariaelisa Graff and Harris, {Sarah E.} and Meian He and Fang-Chi Hsu and John Connell and Smith, {Jennifer A.} and Rao, {Dabeeru C.} and Loos, {Ruth J. F.}",

note = "The present work was largely supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305).",

year = "2019",

month = jan,

day = "22",

doi = "10.1038/s41467-018-08008-w",

language = "English",

volume = "10",

pages = "1--11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

LifeLines Cohort Study, Kilpeläinen, TO, Bentley, AR, Noordam, R, Sung, YJ, Schwander, K, Winkler, TW, Jakupović, H, Chasman, DI, Manning, A, Ntalla, I, Aschard, H, Brown, MR, de Las Fuentes, L, Franceschini, N, Guo, X, Vojinovic, D, Aslibekyan, S, Feitosa, MF, Kho, M, Musani, SK, Richard, M, Wang, H, Wang, Z, Bartz, TM, Bielak, LF, Campbell, A, Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, ARVR, Li, C, Lohman, KK, Marten, J, Sim, X, Smith, AV, Tajuddin, SM, Alver, M, Amini, M, Boissel, M, Chai, JF, Chen, X, Divers, J, Evangelou, E, Gao, C, Graff, M, Harris, SE, He, M, Hsu, F-C, Connell, J, Smith, JA, Rao, DC & Loos, RJF 2019, 'Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity', Nature Communications, vol. 10, no. 1, 376, pp. 1-11. https://doi.org/10.1038/s41467-018-08008-w

TY - JOUR

T1 - Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

AU - LifeLines Cohort Study

AU - Kilpeläinen, Tuomas O.

AU - Bentley, Amy R.

AU - Noordam, Raymond

AU - Sung, Yun Ju

AU - Schwander, Karen

AU - Winkler, Thomas W.

AU - Jakupović, Hermina

AU - Chasman, Daniel I.

AU - Manning, Alisa

AU - Ntalla, Ioanna

AU - Aschard, Hugues

AU - Brown, Michael R.

AU - de Las Fuentes, Lisa

AU - Franceschini, Nora

AU - Guo, Xiuqing

AU - Vojinovic, Dina

AU - Aslibekyan, Stella

AU - Feitosa, Mary F.

AU - Kho, Minjung

AU - Musani, Solomon K.

AU - Richard, Melissa

AU - Wang, Heming

AU - Wang, Zhe

AU - Bartz, Traci M.

AU - Bielak, Lawrence F.

AU - Campbell, Archie

AU - Dorajoo, Rajkumar

AU - Fisher, Virginia

AU - Hartwig, Fernando P.

AU - Horimoto, Andrea R. V. R.

AU - Li, Changwei

AU - Lohman, Kurt K.

AU - Marten, Jonathan

AU - Sim, Xueling

AU - Smith, Albert V.

AU - Tajuddin, Salman M.

AU - Alver, Maris

AU - Amini, Marzyeh

AU - Boissel, Mathilde

AU - Chai, Jin Fang

AU - Chen, Xu

AU - Divers, Jasmin

AU - Evangelou, Evangelos

AU - Gao, Chuan

AU - Graff, Mariaelisa

AU - Harris, Sarah E.

AU - He, Meian

AU - Hsu, Fang-Chi

AU - Connell, John

AU - Smith, Jennifer A.

AU - Rao, Dabeeru C.

AU - Loos, Ruth J. F.

N1 - The present work was largely supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305).

PY - 2019/1/22

Y1 - 2019/1/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85060388984&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-08008-w

DO - 10.1038/s41467-018-08008-w

M3 - Article

C2 - 30670697

SN - 2041-1723

VL - 10

SP - 1

EP - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 376

ER -

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

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