Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.
Adolescent
Adult
Aged
Aged, 80 and over
Asian People
/ genetics
Black People
/ genetics
Brazil
Calcium-Binding Proteins
/ genetics
Cholesterol
/ blood
Cholesterol, HDL
/ blood
Cholesterol, LDL
/ 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
White People
/ genetics
Young Adult
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 01 2019
22 01 2019
Historique:
received:
06
06
2018
accepted:
07
12
2018
entrez:
24
1
2019
pubmed:
24
1
2019
medline:
7
2
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30670697
doi: 10.1038/s41467-018-08008-w
pii: 10.1038/s41467-018-08008-w
pmc: PMC6342931
doi:
Substances chimiques
CLASP1 protein, human
0
CNTNAP2 protein, human
0
Calcium-Binding Proteins
0
Cholesterol, HDL
0
Cholesterol, LDL
0
LHX1 protein, human
0
LIM-Homeodomain Proteins
0
Lipids
0
Membrane Proteins
0
Microtubule-Associated Proteins
0
Muscle Proteins
0
Nerve Tissue Proteins
0
Transcription Factors
0
Triglycerides
0
syntrophin alpha1
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
376Subventions
Organisme : Medical Research Council
ID : MC_UU_12015/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL142302
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020541
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020572
Pays : United States
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/F019394/1
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK093757
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007417
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL120393
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL046380
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL136700
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG009740
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL120393
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL113338
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK072193
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107786
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA173640
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK079626
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056341
Pays : United States
Organisme : Medical Research Council
ID : MR/L01341X/1
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK075787
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL119443
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL118305
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK062370
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135818
Pays : United States
Organisme : Medical Research Council
ID : MR/R023484/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG055406
Pays : United States
Organisme : Medical Research Council
ID : MR/L01632X/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : U01 HL137162
Pays : United States
Organisme : NCRR NIH HHS
ID : M01 RR000032
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : U01 DK062370
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK091317
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA196569
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA182910
Pays : United States
Organisme : NICHD NIH HHS
ID : P2C HD050924
Pays : United States
Organisme : NHLBI NIH HHS
ID : K01 HL135405
Pays : United States
Organisme : Medical Research Council
ID : MR/K026992/1
Pays : United Kingdom
Investigateurs
Behrooz Z Alizadeh
(BZ)
H Marike Boezen
(HM)
Lude Franke
(L)
Gerjan Navis
(G)
Marianne Rots
(M)
Morris Swertz
(M)
Bruce H R Wolffenbuttel
(BHR)
Cisca Wijmenga
(C)
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