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

doi:10.1038/s41467-018-08008-w

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

Research output: Contribution to journal › Article › Academic › peer-review

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)	376
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-08008-w
Publication status	Published - 22 Jan 2019
Externally published	Yes

Keywords

Adolescent
Adult
Aged
Aged, 80 and over
Asians/genetics
Blacks/genetics
Brazil
Calcium-Binding Proteins/genetics
Cholesterol, HDL/blood
Cholesterol, LDL/blood
Cholesterol/blood
Exercise
Female
Genetic Loci/genetics
Genome-Wide Association Study
Genotype
Hispanic or Latino/genetics
Humans
LIM-Homeodomain Proteins/genetics
Lipid Metabolism/genetics
Lipids/blood
Male
Membrane Proteins/genetics
Microtubule-Associated Proteins/genetics
Middle Aged
Muscle Proteins/genetics
Nerve Tissue Proteins/genetics
Transcription Factors/genetics
Triglycerides/blood
Whites/genetics
Young Adult

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10.1038/s41467-018-08008-w

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@article{84e40198861c415aae4f010c888c53ea,

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.",

keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Asians/genetics, Blacks/genetics, Brazil, Calcium-Binding Proteins/genetics, Cholesterol, HDL/blood, Cholesterol, LDL/blood, Cholesterol/blood, Exercise, Female, Genetic Loci/genetics, Genome-Wide Association Study, Genotype, Hispanic or Latino/genetics, Humans, LIM-Homeodomain Proteins/genetics, Lipid Metabolism/genetics, Lipids/blood, Male, Membrane Proteins/genetics, Microtubule-Associated Proteins/genetics, Middle Aged, Muscle Proteins/genetics, Nerve Tissue Proteins/genetics, Transcription Factors/genetics, Triglycerides/blood, Whites/genetics, Young Adult",

author = "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 Raha Pazoki and {van der Ende}, {M Yldau} and {van der Harst}, Pim",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = jan,

day = "22",

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

language = "English",

volume = "10",

pages = "376",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

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TY - JOUR

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

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 - Pazoki, Raha

AU - van der Ende, M Yldau

AU - van der Harst, Pim

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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Asians/genetics

KW - Blacks/genetics

KW - Brazil

KW - Calcium-Binding Proteins/genetics

KW - Cholesterol, HDL/blood

KW - Cholesterol, LDL/blood

KW - Cholesterol/blood

KW - Exercise

KW - Female

KW - Genetic Loci/genetics

KW - Genome-Wide Association Study

KW - Genotype

KW - Hispanic or Latino/genetics

KW - Humans

KW - LIM-Homeodomain Proteins/genetics

KW - Lipid Metabolism/genetics

KW - Lipids/blood

KW - Male

KW - Membrane Proteins/genetics

KW - Microtubule-Associated Proteins/genetics

KW - Middle Aged

KW - Muscle Proteins/genetics

KW - Nerve Tissue Proteins/genetics

KW - Transcription Factors/genetics

KW - Triglycerides/blood

KW - Whites/genetics

KW - Young Adult

U2 - 10.1038/s41467-018-08008-w

DO - 10.1038/s41467-018-08008-w

M3 - Article

C2 - 30670697

SN - 2041-1723

VL - 10

SP - 376

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

Abstract

Keywords

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