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

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

doi:10.1038/s41467-018-08008-w

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

Details

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Serval ID

serval:BIB_1B8EF42248BA

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

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

Journal

Nature communications

Author(s)

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

Working group(s)

Lifelines Cohort Study

Contributor(s)

Alizadeh B.Z., Boezen H.M., Franke L., Navis G., Rots M., Swertz M., Wolffenbuttel BHR, Wijmenga C.

ISSN

2041-1723 (Electronic)

ISSN-L

2041-1723

Publication state

Published

Issued date

22/01/2019

Peer-reviewed

Oui

Volume

Number

Pages

376

Language

english

Notes

Publication types: Journal Article ; Research Support, N.I.H., Extramural
Publication Status: epublish

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, African Continental Ancestry Group/genetics, Aged, Aged, 80 and over, Asian Continental Ancestry Group/genetics, Brazil, Calcium-Binding Proteins/genetics, Cholesterol/blood, Cholesterol, HDL/blood, Cholesterol, HDL/genetics, Cholesterol, LDL/blood, Cholesterol, LDL/genetics, European Continental Ancestry Group/genetics, Exercise, Female, Genetic Loci/genetics, Genome-Wide Association Study, Genotype, Hispanic Americans/genetics, Humans, LIM-Homeodomain Proteins/genetics, Lipid Metabolism/genetics, Lipids/blood, Lipids/genetics, Male, Membrane Proteins/genetics, Microtubule-Associated Proteins/genetics, Middle Aged, Muscle Proteins/genetics, Nerve Tissue Proteins/genetics, Transcription Factors/genetics, Triglycerides/blood, Triglycerides/genetics, Young Adult

URN

urn:nbn:ch:serval-BIB_1B8EF42248BA4

OAI-PMH

oai:serval.unil.ch:BIB_1B8EF42248BA

DOI

10.1038/s41467-018-08008-w

Pubmed

30670697

Web of science

000456286400004

Open Access

Yes