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


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.

SUBMITTER: Kilpelainen TO 

PROVIDER: S-EPMC6342931 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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

Kilpeläinen Tuomas O TO   Bentley Amy R AR   Noordam Raymond R   Sung Yun Ju YJ   Schwander Karen K   Winkler Thomas W TW   Jakupović Hermina H   Chasman Daniel I DI   Manning Alisa A   Ntalla Ioanna I   Aschard Hugues H   Brown Michael R MR   de las Fuentes Lisa L   Franceschini Nora N   Guo Xiuqing X   Vojinovic Dina D   Aslibekyan Stella S   Feitosa Mary F MF   Kho Minjung M   Musani Solomon K SK   Richard Melissa M   Wang Heming H   Wang Zhe Z   Bartz Traci M TM   Bielak Lawrence F LF   Campbell Archie A   Dorajoo Rajkumar R   Fisher Virginia V   Hartwig Fernando P FP   Horimoto Andrea R V R ARVR   Li Changwei C   Lohman Kurt K KK   Marten Jonathan J   Sim Xueling X   Smith Albert V AV   Tajuddin Salman M SM   Alver Maris M   Amini Marzyeh M   Boissel Mathilde M   Chai Jin Fang JF   Chen Xu X   Divers Jasmin J   Evangelou Evangelos E   Gao Chuan C   Graff Mariaelisa M   Harris Sarah E SE   He Meian M   Hsu Fang-Chi FC   Jackson Anne U AU   Zhao Jing Hua JH   Kraja Aldi T AT   Kühnel Brigitte B   Laguzzi Federica F   Lyytikäinen Leo-Pekka LP   Nolte Ilja M IM   Rauramaa Rainer R   Riaz Muhammad M   Robino Antonietta A   Rueedi Rico R   Stringham Heather M HM   Takeuchi Fumihiko F   van der Most Peter J PJ   Varga Tibor V TV   Verweij Niek N   Ware Erin B EB   Wen Wanqing W   Li Xiaoyin X   Yanek Lisa R LR   Amin Najaf N   Arnett Donna K DK   Boerwinkle Eric E   Brumat Marco M   Cade Brian B   Canouil Mickaël M   Chen Yii-Der Ida YI   Concas Maria Pina MP   Connell John J   de Mutsert Renée R   de Silva H Janaka HJ   de Vries Paul S PS   Demirkan Ayşe A   Ding Jingzhong J   Eaton Charles B CB   Faul Jessica D JD   Friedlander Yechiel Y   Gabriel Kelley P KP   Ghanbari Mohsen M   Giulianini Franco F   Gu Chi Charles CC   Gu Dongfeng D   Harris Tamara B TB   He Jiang J   Heikkinen Sami S   Heng Chew-Kiat CK   Hunt Steven C SC   Ikram M Arfan MA   Jonas Jost B JB   Koh Woon-Puay WP   Komulainen Pirjo P   Krieger Jose E JE   Kritchevsky Stephen B SB   Kutalik Zoltán Z   Kuusisto Johanna J   Langefeld Carl D CD   Langenberg Claudia C   Launer Lenore J LJ   Leander Karin K   Lemaitre Rozenn N RN   Lewis Cora E CE   Liang Jingjing J   Liu Jianjun J   Mägi Reedik R   Manichaikul Ani A   Meitinger Thomas T   Metspalu Andres A   Milaneschi Yuri Y   Mohlke Karen L KL   Mosley Thomas H TH   Murray Alison D AD   Nalls Mike A MA   Nang Ei-Ei Khaing EK   Nelson Christopher P CP   Nona Sotoodehnia S   Norris Jill M JM   Nwuba Chiamaka Vivian CV   O'Connell Jeff J   Palmer Nicholette D ND   Papanicolau George J GJ   Pazoki Raha R   Pedersen Nancy L NL   Peters Annette A   Peyser Patricia A PA   Polasek Ozren O   Porteous David J DJ   Poveda Alaitz A   Raitakari Olli T OT   Rich Stephen S SS   Risch Neil N   Robinson Jennifer G JG   Rose Lynda M LM   Rudan Igor I   Schreiner Pamela J PJ   Scott Robert A RA   Sidney Stephen S SS   Sims Mario M   Smith Jennifer A JA   Snieder Harold H   Sofer Tamar T   Starr John M JM   Sternfeld Barbara B   Strauch Konstantin K   Tang Hua H   Taylor Kent D KD   Tsai Michael Y MY   Tuomilehto Jaakko J   Uitterlinden André G AG   van der Ende M Yldau MY   van Heemst Diana D   Voortman Trudy T   Waldenberger Melanie M   Wennberg Patrik P   Wilson Gregory G   Xiang Yong-Bing YB   Yao Jie J   Yu Caizheng C   Yuan Jian-Min JM   Zhao Wei W   Zonderman Alan B AB   Becker Diane M DM   Boehnke Michael M   Bowden Donald W DW   de Faire Ulf U   Deary Ian J IJ   Elliott Paul P   Esko Tõnu T   Freedman Barry I BI   Froguel Philippe P   Gasparini Paolo P   Gieger Christian C   Kato Norihiro N   Laakso Markku M   Lakka Timo A TA   Lehtimäki Terho T   Magnusson Patrik K E PKE   Oldehinkel Albertine J AJ   Penninx Brenda W J H BWJH   Samani Nilesh J NJ   Shu Xiao-Ou XO   van der Harst Pim P   Van Vliet-Ostaptchouk Jana V JV   Vollenweider Peter P   Wagenknecht Lynne E LE   Wang Ya X YX   Wareham Nicholas J NJ   Weir David R DR   Wu Tangchun T   Zheng Wei W   Zhu Xiaofeng X   Evans Michele K MK   Franks Paul W PW   Gudnason Vilmundur V   Hayward Caroline C   Horta Bernardo L BL   Kelly Tanika N TN   Liu Yongmei Y   North Kari E KE   Pereira Alexandre C AC   Ridker Paul M PM   Tai E Shyong ES   van Dam Rob M RM   Fox Ervin R ER   Kardia Sharon L R SLR   Liu Ching-Ti CT   Mook-Kanamori Dennis O DO   Province Michael A MA   Redline Susan S   van Duijn Cornelia M CM   Rotter Jerome I JI   Kooperberg Charles B CB   Gauderman W James WJ   Psaty Bruce M BM   Rice Kenneth K   Munroe Patricia B PB   Fornage Myriam M   Cupples L Adrienne LA   Rotimi Charles N CN   Morrison Alanna C AC   Rao Dabeeru C DC   Loos Ruth J F RJF  

Nature communications 20190122 1


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 f  ...[more]

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