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

Publication ,  Journal Article
Kilpeläinen, TO; Bentley, AR; Noordam, R; Sung, YJ; Schwander, K; Winkler, TW; Jakupović, H; Chasman, DI; Manning, A; Ntalla, I; Aschard, H ...
Published in: Nat Commun
January 22, 2019

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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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 22, 2019

Volume

10

Issue

1

Start / End Page

376

Location

England

Related Subject Headings

  • Young Adult
  • White People
  • Triglycerides
  • Transcription Factors
  • Nerve Tissue Proteins
  • Muscle Proteins
  • Middle Aged
  • Microtubule-Associated Proteins
  • Membrane Proteins
  • Male
 

Citation

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Kilpeläinen, T. O., Bentley, A. R., Noordam, R., Sung, Y. J., Schwander, K., Winkler, T. W., … Loos, R. J. F. (2019). Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity. Nat Commun, 10(1), 376. https://doi.org/10.1038/s41467-018-08008-w
Kilpeläinen, Tuomas O., Amy R. Bentley, Raymond Noordam, Yun Ju Sung, Karen Schwander, Thomas W. Winkler, Hermina Jakupović, et al. “Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.Nat Commun 10, no. 1 (January 22, 2019): 376. https://doi.org/10.1038/s41467-018-08008-w.
Kilpeläinen TO, Bentley AR, Noordam R, Sung YJ, Schwander K, Winkler TW, et al. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity. Nat Commun. 2019 Jan 22;10(1):376.
Kilpeläinen, Tuomas O., et al. “Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.Nat Commun, vol. 10, no. 1, Jan. 2019, p. 376. Pubmed, doi:10.1038/s41467-018-08008-w.
Kilpeläinen TO, Bentley AR, Noordam R, Sung YJ, Schwander K, Winkler TW, Jakupović H, Chasman DI, Manning A, Ntalla I, Aschard H, Brown MR, de Las Fuentes L, Franceschini N, Guo X, Vojinovic D, Aslibekyan S, Feitosa MF, Kho M, Musani SK, Richard M, Wang H, Wang Z, Bartz TM, Bielak LF, Campbell A, Dorajoo R, Fisher V, Hartwig FP, Horimoto ARVR, Li C, Lohman KK, Marten J, Sim X, Smith AV, Tajuddin SM, Alver M, Amini M, Boissel M, Chai JF, Chen X, Divers J, Evangelou E, Gao C, Graff M, Harris SE, He M, Hsu F-C, Jackson AU, Zhao JH, Kraja AT, Kühnel B, Laguzzi F, Lyytikäinen L-P, Nolte IM, Rauramaa R, Riaz M, Robino A, Rueedi R, Stringham HM, Takeuchi F, van der Most PJ, Varga TV, Verweij N, Ware EB, Wen W, Li X, Yanek LR, Amin N, Arnett DK, Boerwinkle E, Brumat M, Cade B, Canouil M, Chen Y-DI, Concas MP, Connell J, de Mutsert R, de Silva HJ, de Vries PS, Demirkan A, Ding J, Eaton CB, Faul JD, Friedlander Y, Gabriel KP, Ghanbari M, Giulianini F, Gu CC, Gu D, Harris TB, He J, Heikkinen S, Heng C-K, Hunt SC, Ikram MA, Jonas JB, Koh W-P, Komulainen P, Krieger JE, Kritchevsky SB, Kutalik Z, Kuusisto J, Langefeld CD, Langenberg C, Launer LJ, Leander K, Lemaitre RN, Lewis CE, Liang J, Lifelines Cohort Study, Liu J, Mägi R, Manichaikul A, Meitinger T, Metspalu A, Milaneschi Y, Mohlke KL, Mosley TH, Murray AD, Nalls MA, Nang E-EK, Nelson CP, Nona S, Norris JM, Nwuba CV, O’Connell J, Palmer ND, Papanicolau GJ, Pazoki R, Pedersen NL, Peters A, Peyser PA, Polasek O, Porteous DJ, Poveda A, Raitakari OT, Rich SS, Risch N, Robinson JG, Rose LM, Rudan I, Schreiner PJ, Scott RA, Sidney SS, Sims M, Smith JA, Snieder H, Sofer T, Starr JM, Sternfeld B, Strauch K, Tang H, Taylor KD, Tsai MY, Tuomilehto J, Uitterlinden AG, van der Ende MY, van Heemst D, Voortman T, Waldenberger M, Wennberg P, Wilson G, Xiang Y-B, Yao J, Yu C, Yuan J-M, Zhao W, Zonderman AB, Becker DM, Boehnke M, Bowden DW, de Faire U, Deary IJ, Elliott P, Esko T, Freedman BI, Froguel P, Gasparini P, Gieger C, Kato N, Laakso M, Lakka TA, Lehtimäki T, Magnusson PKE, Oldehinkel AJ, Penninx BWJH, Samani NJ, Shu X-O, van der Harst P, Van Vliet-Ostaptchouk JV, Vollenweider P, Wagenknecht LE, Wang YX, Wareham NJ, Weir DR, Wu T, Zheng W, Zhu X, Evans MK, Franks PW, Gudnason V, Hayward C, Horta BL, Kelly TN, Liu Y, North KE, Pereira AC, Ridker PM, Tai ES, van Dam RM, Fox ER, Kardia SLR, Liu C-T, Mook-Kanamori DO, Province MA, Redline S, van Duijn CM, Rotter JI, Kooperberg CB, Gauderman WJ, Psaty BM, Rice K, Munroe PB, Fornage M, Cupples LA, Rotimi CN, Morrison AC, Rao DC, Loos RJF. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity. Nat Commun. 2019 Jan 22;10(1):376.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

January 22, 2019

Volume

10

Issue

1

Start / End Page

376

Location

England

Related Subject Headings

  • Young Adult
  • White People
  • Triglycerides
  • Transcription Factors
  • Nerve Tissue Proteins
  • Muscle Proteins
  • Middle Aged
  • Microtubule-Associated Proteins
  • Membrane Proteins
  • Male