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 - Hsu, Fang Chi
AU - Jackson, Anne U.
AU - Arnett, Donna K.
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
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.
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U2 - 10.1038/s41467-018-08008-w
DO - 10.1038/s41467-018-08008-w
M3 - Article
C2 - 30670697
AN - SCOPUS:85060388984
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 376
ER -