Abstract
| Original language | English |
|---|---|
| Article number | 376 |
| Number of pages | 11 |
| Journal | Nature Communications |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 22 Jan 2019 |
Keywords
- Adolescent
- Adult
- African Continental Ancestry Group/genetics
- Aged
- Aged, 80 and over
- Asian Continental Ancestry Group/genetics
- Brazil
- Calcium-Binding Proteins/genetics
- Cholesterol, HDL/blood
- Cholesterol, LDL/blood
- Cholesterol/blood
- 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
- Male
- Membrane Proteins/genetics
- Microtubule-Associated Proteins/genetics
- Middle Aged
- Muscle Proteins/genetics
- Nerve Tissue Proteins/genetics
- Transcription Factors/genetics
- Triglycerides/blood
- Young Adult
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- 10.1038/s41467-018-08008-wLicence: CC BY
- Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity. / Kilpeläinen, Tuomas O. (Corresponding Author); Bentley, Amy R.; Noordam, Raymond; Sung, Yun Ju; Schwander, Karen; Winkler, Thomas W.; Jakupović, Hermina; Chasman, Daniel I.; Manning, Alisa; Ntalla, Ioanna; Aschard, Hugues; Brown, Michael R.; de las Fuentes, Lisa; Franceschini, Nora; Guo, Xiuqing; Vojinovic, Dina; Aslibekyan, Stella; Feitosa, Mary F.; Kho, Minjung; Musani, Solomon K.; Richard, Melissa; Wang, Heming; Wang, Zhe; Bartz, Traci M.; Bielak, Lawrence F.; Campbell, Archie; Dorajoo, Rajkumar; Fisher, Virginia; Hartwig, Fernando P.; Horimoto, Andrea R. V. R.; Li, Changwei; Lohman, Kurt K.; Marten, Jonathan; Sim, Xueling; Smith, Albert V.; Tajuddin, Salman M.; Alver, Maris; Amini, Marzyeh; Boissel, Mathilde; Chai, Jin Fang; Chen, Xu; Divers, Jasmin; Evangelou, Evangelos; Gao, Chuan; Graff, Mariaelisa; Harris, Sarah E.; He, Meian; Hsu, Fang-Chi; Jackson, Anne U.; Zhao, Jing Hua; Kraja, Aldi T.; Kühnel, Brigitte; Laguzzi, Federica; Lyytikäinen, Leo-Pekka; Nolte, Ilja M.; Rauramaa, Rainer; Riaz, Muhammad; Robino, Antonietta; Rueedi, Rico; Stringham, Heather M.; Takeuchi, Fumihiko; van der Most, Peter J.; Varga, Tibor V.; Verweij, Niek; Ware, Erin B.; Wen, Wanqing; Li, Xiaoyin; Yanek, Lisa R.; Amin, Najaf; Arnett, Donna K.; Boerwinkle, Eric; Brumat, Marco; Cade, Brian; Canouil, Mickaël; Chen, Yii-Der Ida; Concas, Maria Pina; Connell, John; de Mutsert, Renée; de Silva, H. Janaka; de Vries, Paul S.; Demirkan, Ayşe; Ding, Jingzhong; Eaton, Charles B.; Faul, Jessica D.; Friedlander, Yechiel; Gabriel, Kelley P.; Ghanbari, Mohsen; Giulianini, Franco; Gu, Chi Charles; Gu, Dongfeng; Harris, Tamara B.; He, Jiang; Heikkinen, Sami; Heng, Chew-Kiat; Hunt, Steven C.; Ikram, M. Arfan; Jonas, Jost B.; Koh, Woon-Puay; Komulainen, Pirjo; Krieger, Jose E.; Kritchevsky, Stephen B.; Kutalik, Zoltán; Kuusisto, Johanna; Langefeld, Carl D.; Langenberg, Claudia; Launer, Lenore J.; Leander, Karin; Lemaitre, Rozenn N.; Lewis, Cora E.; Liang, Jingjing; Alizadeh, Behrooz Z.; Boezen, H. Marike; Franke, Lude; Navis, Gerjan; Rots, Marianne; Swertz, Morris; Wolffenbuttel, Bruce H. R.; Wijmenga, Cisca; Liu, Jianjun; Mägi, Reedik; Manichaikul, Ani; Meitinger, Thomas; Metspalu, Andres; Milaneschi, Yuri; Mohlke, Karen L.; Mosley, Thomas H.; Murray, Alison D.; Nalls, Mike A.; Nang, Ei-Ei Khaing; Nelson, Christopher P.; Nona, Sotoodehnia; Norris, Jill M.; Nwuba, Chiamaka Vivian; O’Connell, Jeff; Palmer, Nicholette D.; Papanicolau, George J.; Pazoki, Raha; Pedersen, Nancy L.; Peters, Annette; Peyser, Patricia A.; Polasek, Ozren; Porteous, David J.; Poveda, Alaitz; Raitakari, Olli T.; Rich, Stephen S.; Risch, Neil; Robinson, Jennifer G.; Rose, Lynda M.; Rudan, Igor; Schreiner, Pamela J.; Scott, Robert A.; Sidney, Stephen S.; Sims, Mario; Smith, Jennifer A.; Snieder, Harold; Sofer, Tamar; Starr, John M.; Sternfeld, Barbara; Strauch, Konstantin; Tang, Hua; Taylor, Kent D.; Tsai, Michael Y.; Tuomilehto, Jaakko; Uitterlinden, André G.; van der Ende, M. Yldau; van Heemst, Diana; Voortman, Trudy; Waldenberger, Melanie; Wennberg, Patrik; Wilson, Gregory; Xiang, Yong-Bing; Yao, Jie; Yu, Caizheng; Yuan, Jian-Min; Zhao, Wei; Zonderman, Alan B.; Becker, Diane M.; Boehnke, Michael; Bowden, Donald W.; de Faire, Ulf; Deary, Ian J.; Elliott, Paul; Esko, Tõnu; Freedman, Barry I.; Froguel, Philippe; Gasparini, Paolo; Gieger, Christian; Kato, Norihiro; Laakso, Markku; Lakka, Timo A.; Lehtimäki, Terho; Magnusson, Patrik K. E.; Oldehinkel, Albertine J.; Penninx, Brenda W. J. H.; Samani, Nilesh J.; Shu, Xiao-Ou; van der Harst, Pim; Van Vliet-Ostaptchouk, Jana V.; Vollenweider, Peter; Wagenknecht, Lynne E.; Wang, Ya X.; Wareham, Nicholas J.; Weir, David R.; Wu, Tangchun; Zheng, Wei; Zhu, Xiaofeng; Evans, Michele K.; Franks, Paul W.; Gudnason, Vilmundur; Hayward, Caroline; Horta, Bernardo L.; Kelly, Tanika N.; Liu, Yongmei; North, Kari E.; Pereira, Alexandre C.; Ridker, Paul M.; Tai, E. Shyong; van Dam, Rob M.; Fox, Ervin R.; Kardia, Sharon L. R.; Liu, Ching-Ti; Mook-Kanamori, Dennis O.; Province, Michael A.; Redline, Susan; van Duijn, Cornelia M.; Rotter, Jerome I.; Kooperberg, Charles B.; Gauderman, W. James; Psaty, Bruce M.; Rice, Kenneth; Munroe, Patricia B.; Fornage, Myriam; Cupples, L. Adrienne; Rotimi, Charles N.; Morrison, Alanna C.; Rao, Dabeeru C. (Corresponding Author); Loos, Ruth J. F. (Corresponding Author); Study, Lifelines Cohort.
In: Nature Communications, Vol. 10, No. 1, 376, 22.01.2019.Research output: Contribution to journal › Article › peer-review
}
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 - Zhao, Jing Hua
AU - Kraja, Aldi T.
AU - Kühnel, Brigitte
AU - Laguzzi, Federica
AU - Lyytikäinen, Leo-Pekka
AU - Nolte, Ilja M.
AU - Rauramaa, Rainer
AU - Riaz, Muhammad
AU - Robino, Antonietta
AU - Rueedi, Rico
AU - Stringham, Heather M.
AU - Takeuchi, Fumihiko
AU - van der Most, Peter J.
AU - Varga, Tibor V.
AU - Verweij, Niek
AU - Ware, Erin B.
AU - Wen, Wanqing
AU - Li, Xiaoyin
AU - Yanek, Lisa R.
AU - Amin, Najaf
AU - Arnett, Donna K.
AU - Boerwinkle, Eric
AU - Brumat, Marco
AU - Cade, Brian
AU - Canouil, Mickaël
AU - Chen, Yii-Der Ida
AU - Concas, Maria Pina
AU - Connell, John
AU - de Mutsert, Renée
AU - de Silva, H. Janaka
AU - de Vries, Paul S.
AU - Demirkan, Ayşe
AU - Ding, Jingzhong
AU - Eaton, Charles B.
AU - Faul, Jessica D.
AU - Friedlander, Yechiel
AU - Gabriel, Kelley P.
AU - Ghanbari, Mohsen
AU - Giulianini, Franco
AU - Gu, Chi Charles
AU - Gu, Dongfeng
AU - Harris, Tamara B.
AU - He, Jiang
AU - Heikkinen, Sami
AU - Heng, Chew-Kiat
AU - Hunt, Steven C.
AU - Ikram, M. Arfan
AU - Jonas, Jost B.
AU - Koh, Woon-Puay
AU - Komulainen, Pirjo
AU - Krieger, Jose E.
AU - Kritchevsky, Stephen B.
AU - Kutalik, Zoltán
AU - Kuusisto, Johanna
AU - Langefeld, Carl D.
AU - Langenberg, Claudia
AU - Launer, Lenore J.
AU - Leander, Karin
AU - Lemaitre, Rozenn N.
AU - Lewis, Cora E.
AU - Liang, Jingjing
AU - Alizadeh, Behrooz Z.
AU - Boezen, H. Marike
AU - Franke, Lude
AU - Navis, Gerjan
AU - Rots, Marianne
AU - Swertz, Morris
AU - Wolffenbuttel, Bruce H. R.
AU - Wijmenga, Cisca
AU - Liu, Jianjun
AU - Mägi, Reedik
AU - Manichaikul, Ani
AU - Meitinger, Thomas
AU - Metspalu, Andres
AU - Milaneschi, Yuri
AU - Mohlke, Karen L.
AU - Mosley, Thomas H.
AU - Murray, Alison D.
AU - Nalls, Mike A.
AU - Nang, Ei-Ei Khaing
AU - Nelson, Christopher P.
AU - Nona, Sotoodehnia
AU - Norris, Jill M.
AU - Nwuba, Chiamaka Vivian
AU - O’Connell, Jeff
AU - Palmer, Nicholette D.
AU - Papanicolau, George J.
AU - Pazoki, Raha
AU - Pedersen, Nancy L.
AU - Peters, Annette
AU - Peyser, Patricia A.
AU - Polasek, Ozren
AU - Porteous, David J.
AU - Poveda, Alaitz
AU - Raitakari, Olli T.
AU - Rich, Stephen S.
AU - Risch, Neil
AU - Robinson, Jennifer G.
AU - Rose, Lynda M.
AU - Rudan, Igor
AU - Schreiner, Pamela J.
AU - Scott, Robert A.
AU - Sidney, Stephen S.
AU - Sims, Mario
AU - Smith, Jennifer A.
AU - Snieder, Harold
AU - Sofer, Tamar
AU - Starr, John M.
AU - Sternfeld, Barbara
AU - Strauch, Konstantin
AU - Tang, Hua
AU - Taylor, Kent D.
AU - Tsai, Michael Y.
AU - Tuomilehto, Jaakko
AU - Uitterlinden, André G.
AU - van der Ende, M. Yldau
AU - van Heemst, Diana
AU - Voortman, Trudy
AU - Waldenberger, Melanie
AU - Wennberg, Patrik
AU - Wilson, Gregory
AU - Xiang, Yong-Bing
AU - Yao, Jie
AU - Yu, Caizheng
AU - Yuan, Jian-Min
AU - Zhao, Wei
AU - Zonderman, Alan B.
AU - Becker, Diane M.
AU - Boehnke, Michael
AU - Bowden, Donald W.
AU - de Faire, Ulf
AU - Deary, Ian J.
AU - Elliott, Paul
AU - Esko, Tõnu
AU - Freedman, Barry I.
AU - Froguel, Philippe
AU - Gasparini, Paolo
AU - Gieger, Christian
AU - Kato, Norihiro
AU - Laakso, Markku
AU - Lakka, Timo A.
AU - Lehtimäki, Terho
AU - Magnusson, Patrik K. E.
AU - Oldehinkel, Albertine J.
AU - Penninx, Brenda W. J. H.
AU - Samani, Nilesh J.
AU - Shu, Xiao-Ou
AU - van der Harst, Pim
AU - Van Vliet-Ostaptchouk, Jana V.
AU - Vollenweider, Peter
AU - Wagenknecht, Lynne E.
AU - Wang, Ya X.
AU - Wareham, Nicholas J.
AU - Weir, David R.
AU - Wu, Tangchun
AU - Zheng, Wei
AU - Zhu, Xiaofeng
AU - Evans, Michele K.
AU - Franks, Paul W.
AU - Gudnason, Vilmundur
AU - Hayward, Caroline
AU - Horta, Bernardo L.
AU - Kelly, Tanika N.
AU - Liu, Yongmei
AU - North, Kari E.
AU - Pereira, Alexandre C.
AU - Ridker, Paul M.
AU - Tai, E. Shyong
AU - van Dam, Rob M.
AU - Fox, Ervin R.
AU - Kardia, Sharon L. R.
AU - Liu, Ching-Ti
AU - Mook-Kanamori, Dennis O.
AU - Province, Michael A.
AU - Redline, Susan
AU - van Duijn, Cornelia M.
AU - Rotter, Jerome I.
AU - Kooperberg, Charles B.
AU - Gauderman, W. James
AU - Psaty, Bruce M.
AU - Rice, Kenneth
AU - Munroe, Patricia B.
AU - Fornage, Myriam
AU - Cupples, L. Adrienne
AU - Rotimi, Charles N.
AU - Morrison, Alanna C.
AU - Rao, Dabeeru C.
AU - Loos, Ruth J. F.
AU - Study, Lifelines Cohort
N1 - 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.
PY - 2019/1/22
Y1 - 2019/1/22
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.
KW - Adolescent
KW - Adult
KW - African Continental Ancestry Group/genetics
KW - Aged
KW - Aged, 80 and over
KW - Asian Continental Ancestry Group/genetics
KW - Brazil
KW - Calcium-Binding Proteins/genetics
KW - Cholesterol, HDL/blood
KW - Cholesterol, LDL/blood
KW - Cholesterol/blood
KW - European Continental Ancestry Group/genetics
KW - Exercise
KW - Female
KW - Genetic Loci/genetics
KW - Genome-Wide Association Study
KW - Genotype
KW - Hispanic Americans/genetics
KW - Humans
KW - LIM-Homeodomain Proteins/genetics
KW - Lipid Metabolism/genetics
KW - Lipids/blood
KW - Male
KW - Membrane Proteins/genetics
KW - Microtubule-Associated Proteins/genetics
KW - Middle Aged
KW - Muscle Proteins/genetics
KW - Nerve Tissue Proteins/genetics
KW - Transcription Factors/genetics
KW - Triglycerides/blood
KW - Young Adult
UR - http://www.scopus.com/inward/record.url?scp=85060388984&partnerID=8YFLogxK
UR - http://www.mendeley.com/research/multiancestry-study-blood-lipid-levels-identifies-four-loci-interacting-physical-activity
U2 - 10.1038/s41467-018-08008-w
DO - 10.1038/s41467-018-08008-w
M3 - Article
C2 - 30670697
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 376
ER -