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

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; Study, Lifelines Cohort; 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

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

journal contribution

posted on 2019-09-18, 11:03 authored by TO Kilpeläinen, AR Bentley, R Noordam, YJ Sung, K Schwander, TW Winkler, H Jakupović, DI Chasman, A Manning, I Ntalla, H Aschard, MR Brown, L de Las Fuentes, N Franceschini, X Guo, D Vojinovic, S Aslibekyan, MF Feitosa, M Kho, SK Musani, M Richard, H Wang, Z Wang, TM Bartz, LF Bielak, A Campbell, R Dorajoo, V Fisher, FP Hartwig, ARVR Horimoto, C Li, KK Lohman, J Marten, X Sim, AV Smith, SM Tajuddin, M Alver, M Amini, M Boissel, JF Chai, X Chen, J Divers, E Evangelou, C Gao, M Graff, SE Harris, M He, F-C Hsu, AU Jackson, JH Zhao, AT Kraja, B Kühnel, F Laguzzi, L-P Lyytikäinen, IM Nolte, R Rauramaa, M Riaz, A Robino, R Rueedi, HM Stringham, F Takeuchi, PJ van der Most, TV Varga, N Verweij, EB Ware, W Wen, X Li, LR Yanek, N Amin, DK Arnett, E Boerwinkle, M Brumat, B Cade, M Canouil, Y-DI Chen, MP Concas, J Connell, R de Mutsert, HJ de Silva, PS de Vries, A Demirkan, J Ding, CB Eaton, JD Faul, Y Friedlander, KP Gabriel, M Ghanbari, F Giulianini, CC Gu, D Gu, TB Harris, J He, S Heikkinen, C-K Heng, SC Hunt, MA Ikram, JB Jonas, W-P Koh, P Komulainen, JE Krieger, SB Kritchevsky, Z Kutalik, J Kuusisto, CD Langefeld, C Langenberg, LJ Launer, K Leander, RN Lemaitre, CE Lewis, J Liang, Lifelines Cohort Study, J Liu, R Mägi, A Manichaikul, T Meitinger, A Metspalu, Y Milaneschi, KL Mohlke, TH Mosley, AD Murray, MA Nalls, E-EK Nang, CP Nelson, S Nona, JM Norris, CV Nwuba, J O'Connell, ND Palmer, GJ Papanicolau, R Pazoki, NL Pedersen, A Peters, PA Peyser, O Polasek, DJ Porteous, A Poveda, OT Raitakari, SS Rich, N Risch, JG Robinson, LM Rose, I Rudan, PJ Schreiner, RA Scott, SS Sidney, M Sims, JA Smith, H Snieder, T Sofer, JM Starr, B Sternfeld, K Strauch, H Tang, KD Taylor, MY Tsai, J Tuomilehto, AG Uitterlinden, MY van der Ende, D van Heemst, T Voortman, M Waldenberger, P Wennberg, G Wilson, Y-B Xiang, J Yao, C Yu, J-M Yuan, W Zhao, AB Zonderman, DM Becker, M Boehnke, DW Bowden, U de Faire, IJ Deary, P Elliott, T Esko, BI Freedman, P Froguel, P Gasparini, C Gieger, N Kato, M Laakso, TA Lakka, T Lehtimäki, PKE Magnusson, AJ Oldehinkel, BWJH Penninx, NJ Samani, X-O Shu, P van der Harst, JV Van Vliet-Ostaptchouk, P Vollenweider, LE Wagenknecht, YX Wang, NJ Wareham, DR Weir, T Wu, W Zheng, X Zhu, MK Evans, PW Franks, V Gudnason, C Hayward, BL Horta, TN Kelly, Y Liu, KE North, AC Pereira, PM Ridker, ES Tai, RM van Dam, ER Fox, SLR Kardia, C-T Liu, DO Mook-Kanamori, MA Province, S Redline, CM van Duijn, JI Rotter, CB Kooperberg, WJ Gauderman, BM Psaty, K Rice, PB Munroe, M Fornage, LA Cupples, CN Rotimi, AC Morrison, DC Rao, RJF Loos

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.

Funding

The present work was largely supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305). The full list of acknowledgments appears in the Supplementary Notes 3 and 4.

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Nature Communications, 2019, volume 10, Article number: 376

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/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciences

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Nature Communications

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Nature Research (part of Springer Nature)

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2041-1723

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2018-12-07

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2019

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2019-09-18

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https://doi.org/10.1038/s41467-018-08008-w

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https://www.nature.com/articles/s41467-018-08008-w

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Supplementary Information accompanies this paper at https://doi.org/10.1038/s41467-018-08008-w

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en

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https://leicester.figshare.com/account/articles/10197491

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Cardiovascular genetics Dyslipidaemias Genome-wide association studies

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

Funding

The present work was largely supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305). The full list of acknowledgments appears in the Supplementary Notes 3 and 4.

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