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.

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

Robino, Antonietta;Brumat, Marco;Concas, Maria Pina;Gasparini, Paolo
;
2019-01-01

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.
2019
Pubblicato
https://www.nature.com/articles/s41467-018-08008-w
File in questo prodotto:
File Dimensione Formato  
s41467-018-08008-w.pdf

accesso aperto

Tipologia: Documento in Versione Editoriale
Licenza: Creative commons
Dimensione 1.75 MB
Formato Adobe PDF
1.75 MB Adobe PDF Visualizza/Apri
Supplementary information.pdf

accesso aperto

Tipologia: Altro materiale allegato
Licenza: Creative commons
Dimensione 1.04 MB
Formato Adobe PDF
1.04 MB Adobe PDF Visualizza/Apri
Description of Additional Supplementary Files.pdf

accesso aperto

Tipologia: Altro materiale allegato
Licenza: Creative commons
Dimensione 19.76 kB
Formato Adobe PDF
19.76 kB Adobe PDF Visualizza/Apri
Peer review file.pdf

accesso aperto

Tipologia: Altro materiale allegato
Licenza: Creative commons
Dimensione 339.57 kB
Formato Adobe PDF
339.57 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2935005
Citazioni
  • ???jsp.display-item.citation.pmc??? 39
  • Scopus 52
  • ???jsp.display-item.citation.isi??? 50
social impact