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

Liang J.; Strauch K.; Eaton C.B.; Freedman B.I.; Lewis C.E.; Kritchevsky S.B.; Langefeld C.D.; Jakupović H.; Loos R.J.F.; Lifelines Cohort Study; Tang H.; Li X.; Sidney S.S.; Zhao W.; Takeuchi F.; Harris T.B.; Shu X.-O.; Yao J.; Boissel M.; Ridker P.M.; Campbell A.; Porteous D.J.; Robino A.; Van Vliet-Ostaptchouk J.V.; Nang E.-E.K.; Tai E.S.; Komulainen P.; Horta B.L.; Yanek L.R.; Wen W.; Musani S.K.; Hsu F.-C.; Franceschini N.; Pazoki R.; Evangelou E.; Rudan I.; Yuan J.-M.; Morrison A.C.; Jonas J.B.; Hunt S.C.; Ikram M.A.; Launer L.J.; Pereira A.C.; Krieger J.E.; Chasman D.I.; Riaz M.; Ntalla I.; Polasek O.; Amini M.; Vojinovic D.; Tuomilehto J.; Cupples L.A.; Arnett D.K.; Hayward C.; Wang H.; Leander K.; Palmer N.D.; Murray A.D.; Verweij N.; Sung Y.J.; Rots M.; Ding J.; van Heemst D.; Voortman T.; Manichaikul A.; Becker D.M.; Tsai M.Y.; Friedlander Y.; Horimoto A.R.V.R.; Samani N.J.; Wareham N.J.; van der Harst P.; Giulianini F.; Tajuddin S.M.; Nelson C.P.; Franks P.W.; Demirkan A.; Metspalu A.; Smith A.V.; Varga T.V.; Gudnason V.; de Faire U.; Nolte I.M.; van der Most P.J.; Scott R.A.; Meitinger T.; Kuusisto J.; Laakso M.; Liu Y.; Raitakari O.T.; Mohlke K.L.; Xiang Y.-B.; Redline S.; Divers J.; Graff M.; Kelly T.N.; de las Fuentes L.; Province M.A.; Concas M.P.; Rose L.M.; Wagenknecht L.E.; Zonderman A.B.; Gu D.; Sims M.; Risch N.; van Duijn C.M.; Ware E.B.; Chai J.F.; Milaneschi Y.; Winkler T.W.; de Mutsert R.; Penninx B.W.J.H.; Gieger C.; Harris S.E.; Rice K.; Heng C.-K.; Boezen H.M.; Lakka T.A.; Ghanbari M.; Munroe P.B.; Wennberg P.; Kutalik Z.; Navis G.; Vollenweider P.; Franke L.; Kato N.; Bielak L.F.; Boerwinkle E.; Jr.; Guo X.; Kooperberg C.B.; de Vries P.S.; Richard M.; Wolffenbuttel B.H.R.; Wang Y.X.; Liu C.-T.; Robinson J.G.; Froguel P.; Amin N.; Rao D.C.; van der Ende M.Y.; Kardia S.L.R.; Manning A.; Zhao J.H.; Brown M.R.; Kühnel B.; Mägi R.; Gabriel K.P.; Faul J.D.; He M.; Nalls M.A.; Sofer T.; de Silva H.J.; Dorajoo R.; Noordam R.; Lohman K.K.; Deary I.J.; Starr J.M.; Alver M.; Heikkinen S.; Sim X.; Aslibekyan S.; Cade B.; Schwander K.; O’Connell J.; Marten J.; Oldehinkel A.J.; Wang Z.; Psaty B.M.; Nona S.; Gasparini P.; Lyytikäinen L.-P.; Gauderman W.J.; Uitterlinden A.G.; Boehnke M.; Bartz T.M.; Norris J.M.; Connell J.; Kraja A.T.; Wilson G.; Gao C.; Nwuba C.V.; Taylor K.D.; Smith J.A.; Elliott P.; Aschard H.; Fisher V.; Yu C.; He J.; Poveda A.; Rauramaa R.; Kilpeläinen T.O.; Bentley A.R.; van Dam R.M.; Mosley T.H.; Lemaitre R.N.; Hartwig F.P.; Papanicolau G.J.; Mook-Kanamori D.O.; Koh W.-P.; Pedersen N.L.; Peters A.; Rich S.S.; Jackson A.U.; Chen Y.-D.I.; Kho M.; Sternfeld B.; Magnusson P.K.E.; Rueedi R.; Feitosa M.F.; Brumat M.; Lehtimäki T.; Canouil M.; North K.E.; Fox E.R.; Rotter J.I.; Esko T.; Weir D.R.; Rotimi C.N.; Stringham H.M.; Chen X.; Zhu X.; Evans M.K.; Bowden D.W.; Liu J.; Snieder H.; Schreiner P.J.; Wu T.; Langenberg C.; Laguzzi F.; Swertz M.; Alizadeh B.Z.; Li C.; Fornage M.; Gu C.C.; Peyser P.A.; Zheng W.; Wijmenga C.; Waldenberger M.
Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Liang J.
Strauch K.
Eaton C.B.
Freedman B.I.
Lewis C.E.
Kritchevsky S.B.
Langefeld C.D.
Jakupović H.
Loos R.J.F.; Lifelines Cohort Study
Tang H.
Li X.
Sidney S.S.
Zhao W.
Takeuchi F.
Harris T.B.
Shu X.-O.
Yao J.
Boissel M.
Ridker P.M.
Campbell A.
Porteous D.J.
Robino A.
Van Vliet-Ostaptchouk J.V.
Nang E.-E.K.
Tai E.S.
Komulainen P.
Horta B.L.
Yanek L.R.
Wen W.
Musani S.K.
Hsu F.-C.
Franceschini N.
Pazoki R.
Evangelou E.
Rudan I.
Yuan J.-M.
Morrison A.C.
Jonas J.B.
Hunt S.C.
Ikram M.A.
Launer L.J.
Pereira A.C.
Krieger J.E.
Chasman D.I.
Riaz M.
Ntalla I.
Polasek O.
Amini M.
Vojinovic D.
Tuomilehto J.
Cupples L.A.
Arnett D.K.
Hayward C.
Wang H.
Leander K.
Palmer N.D.
Murray A.D.
Verweij N.
Sung Y.J.
Rots M.
Ding J.
van Heemst D.
Voortman T.
Manichaikul A.
Becker D.M.
Tsai M.Y.
Friedlander Y.
Horimoto A.R.V.R.
Samani N.J.
Wareham N.J.
van der Harst P.
Giulianini F.
Tajuddin S.M.
Nelson C.P.
Franks P.W.
Demirkan A.
Metspalu A.
Smith A.V.
Varga T.V.
Gudnason V.
de Faire U.
Nolte I.M.
van der Most P.J.
Scott R.A.
Meitinger T.
Kuusisto J.
Laakso M.
Liu Y.
Raitakari O.T.
Mohlke K.L.
Xiang Y.-B.
Redline S.
Divers J.
Graff M.
Kelly T.N.
de las Fuentes L.
Province M.A.
Concas M.P.
Rose L.M.
Wagenknecht L.E.
Zonderman A.B.
Gu D.
Sims M.
Risch N.
van Duijn C.M.
Ware E.B.
Chai J.F.
Milaneschi Y.
Winkler T.W.
de Mutsert R.
Penninx B.W.J.H.
Gieger C.
Harris S.E.
Rice K.
Heng C.-K.
Boezen H.M.
Lakka T.A.
Ghanbari M.
Munroe P.B.
Wennberg P.
Kutalik Z.
Navis G.
Vollenweider P.
Franke L.
Kato N.
Bielak L.F.
Boerwinkle E.
Jr.
Guo X.
Kooperberg C.B.
de Vries P.S.
Richard M.
Wolffenbuttel B.H.R.
Wang Y.X.
Liu C.-T.
Robinson J.G.
Froguel P.
Amin N.
Rao D.C.
van der Ende M.Y.
Kardia S.L.R.
Manning A.
Zhao J.H.
Brown M.R.
Kühnel B.
Mägi R.
Gabriel K.P.
Faul J.D.
He M.
Nalls M.A.
Sofer T.
de Silva H.J.
Dorajoo R.
Noordam R.
Lohman K.K.
Deary I.J.
Starr J.M.
Alver M.
Heikkinen S.
Sim X.
Aslibekyan S.
Cade B.
Schwander K.
O’Connell J.
Marten J.
Oldehinkel A.J.
Wang Z.
Psaty B.M.
Nona S.
Gasparini P.
Lyytikäinen L.-P.
Gauderman W.J.
Uitterlinden A.G.
Boehnke M.
Bartz T.M.
Norris J.M.
Connell J.
Kraja A.T.
Wilson G.
Gao C.
Nwuba C.V.
Taylor K.D.
Smith J.A.
Elliott P.
Aschard H.
Fisher V.
Yu C.
He J.
Poveda A.
Rauramaa R.
Kilpeläinen T.O.
Bentley A.R.
van Dam R.M.
Mosley T.H.
Lemaitre R.N.
Hartwig F.P.
Papanicolau G.J.
Mook-Kanamori D.O.
Koh W.-P.
Pedersen N.L.
Peters A.
Rich S.S.
Jackson A.U.
Chen Y.-D.I.
Kho M.
Sternfeld B.
Magnusson P.K.E.
Rueedi R.
Feitosa M.F.
Brumat M.
Lehtimäki T.
Canouil M.
North K.E.
Fox E.R.
Rotter J.I.
Esko T.
Weir D.R.
Rotimi C.N.
Stringham H.M.
Chen X.
Zhu X.
Evans M.K.
Bowden D.W.
Liu J.
Snieder H.
Schreiner P.J.
Wu T.
Langenberg C.
Laguzzi F.
Swertz M.
Alizadeh B.Z.
Li C.
Fornage M.
Gu C.C.
Peyser P.A.
Zheng W.
Wijmenga C.
Waldenberger M.
Katso/Avaa
Lataukset: 

NATURE PUBLISHING GROUP
doi:10.1038/s41467-018-08008-w
URI
https://www.nature.com/articles/s41467-018-08008-w
Näytä kaikki kuvailutiedot
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042823265
Tiivistelmä
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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