Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Raymond Noordam; Maxime M. Bos; Heming Wang; Thomas W. Winkler; Amy R. Bentley; Tuomas O. Kilpeläinen; Paul S. de Vries; Yun Ju Sung; Karen Schwander; Brian E. Cade; Alisa Manning; Hugues Aschard; Michael R. Brown; Han Chen; Nora Franceschini; Solomon K. Musani; Melissa Richard; Dina Vojinovic; Stella Aslibekyan; Traci M. Bartz; Lisa de las Fuentes; Mary Feitosa; Andrea R. Horimoto; Marjan Ilkov; Minjung Kho; Aldi Kraja; Changwei Li; Elise Lim; Yongmei Liu; Dennis O. Mook-Kanamori; Tuomo Rankinen; Salman M. Tajuddin; Ashley van der Spek; Zhe Wang; Jonathan Marten; Vincent Laville; Maris Alver; Evangelos Evangelou; Maria E. Graff; Meian He; Brigitte Kühnel; Leo Pekka Lyytikäinen; Pedro Marques-Vidal; Ilja M. Nolte; Nicholette D. Palmer; Rainer Rauramaa; Xiao Ou Shu; Harold Snieder; Stefan Weiss; Wanqing Wen; Lisa R. Yanek; Correa Adolfo; Christie Ballantyne; Larry Bielak; Nienke R. Biermasz; Eric Boerwinkle; Niki Dimou; Gudny Eiriksdottir; Chuan Gao; Sina A. Gharib; Daniel J. Gottlieb; José Haba-Rubio; Tamara B. Harris; Sami Heikkinen; Raphaël Heinzer; James E. Hixson; Georg Homuth; M. Arfan Ikram; Pirjo Komulainen; Jose E. Krieger; Jiwon Lee; Jingmin Liu; Kurt K. Lohman; Annemarie I. Luik; Reedik Mägi; Lisa W. Martin; Thomas Meitinger; Andres Metspalu; Yuri Milaneschi; Mike A. Nalls; Jeff O’Connell; Annette Peters; Patricia Peyser; Olli T. Raitakari; Alex P. Reiner; Patrick C.N. Rensen; Treva K. Rice; Stephen S. Rich; Till Roenneberg; Jerome I. Rotter; Pamela J. Schreiner; James Shikany; Stephen S. Sidney; Mario Sims; Colleen M. Sitlani; Tamar Sofer; Konstantin Strauch; Morris A. Swertz; Kent D. Taylor; André G. Uitterlinden; Cornelia M. van Duijn; Henry Völzke; Melanie Waldenberger; Robert B. Wallance; Ko Willems van Dijk; Caizheng Yu; Alan B. Zonderman; Diane M. Becker; Paul Elliott; Tõnu Esko; Christian Gieger; Hans J. Grabe; Timo A. Lakka; Terho Lehtimäki; Kari E. North; Brenda W.J.H. Penninx; Peter Vollenweider; Lynne E. Wagenknecht; Tangchun Wu; Yong Bing Xiang; Wei Zheng; Donna K. Arnett; Claude Bouchard; Michele K. Evans; Vilmundur Gudnason; Sharon Kardia; Tanika N. Kelly; Stephen B. Kritchevsky; Ruth J.F. Loos; Alexandre C. Pereira; Mike Province; Bruce M. Psaty; Charles Rotimi; Xiaofeng Zhu; Najaf Amin; L. Adrienne Cupples; Myriam Fornage; Ervin F. Fox; Xiuqing Guo; W. James Gauderman; Kenneth Rice; Charles Kooperberg; Patricia B. Munroe; Ching Ti Liu; Alanna C. Morrison; Dabeeru C. Rao; Diana van Heemst; Susan Redline

doi:10.1038/s41467-019-12958-0

Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Raymond Noordam, Maxime M. Bos, Heming Wang, Thomas W. Winkler, Amy R. Bentley, Tuomas O. Kilpeläinen, Paul S. de Vries, Yun Ju Sung, Karen Schwander, Brian E. Cade, Alisa Manning, Hugues Aschard, Michael R. Brown, Han Chen, Nora Franceschini, Solomon K. Musani, Melissa Richard, Dina Vojinovic, Stella Aslibekyan, Traci M. BartzLisa de las Fuentes, Mary Feitosa, Andrea R. Horimoto, Marjan Ilkov, Minjung Kho, Aldi Kraja, Changwei Li, Elise Lim, Yongmei Liu, Dennis O. Mook-Kanamori, Tuomo Rankinen, Salman M. Tajuddin, Ashley van der Spek, Zhe Wang, Jonathan Marten, Vincent Laville, Maris Alver, Evangelos Evangelou, Maria E. Graff, Meian He, Brigitte Kühnel, Leo Pekka Lyytikäinen, Pedro Marques-Vidal, Ilja M. Nolte, Nicholette D. Palmer, Rainer Rauramaa, Xiao Ou Shu, Harold Snieder, Stefan Weiss, Wanqing Wen, Lisa R. Yanek, Correa Adolfo, Christie Ballantyne, Larry Bielak, Nienke R. Biermasz, Eric Boerwinkle, Niki Dimou, Gudny Eiriksdottir, Chuan Gao, Sina A. Gharib, Daniel J. Gottlieb, José Haba-Rubio, Tamara B. Harris, Sami Heikkinen, Raphaël Heinzer, James E. Hixson, Georg Homuth, M. Arfan Ikram, Pirjo Komulainen, Jose E. Krieger, Jiwon Lee, Jingmin Liu, Kurt K. Lohman, Annemarie I. Luik, Reedik Mägi, Lisa W. Martin, Thomas Meitinger, Andres Metspalu, Yuri Milaneschi, Mike A. Nalls, Jeff O’Connell, Annette Peters, Patricia Peyser, Olli T. Raitakari, Alex P. Reiner, Patrick C.N. Rensen, Treva K. Rice, Stephen S. Rich, Till Roenneberg, Jerome I. Rotter, Pamela J. Schreiner, James Shikany, Stephen S. Sidney, Mario Sims, Colleen M. Sitlani, Tamar Sofer, Konstantin Strauch, Morris A. Swertz, Kent D. Taylor, André G. Uitterlinden, Cornelia M. van Duijn, Henry Völzke, Melanie Waldenberger, Robert B. Wallance, Ko Willems van Dijk, Caizheng Yu, Alan B. Zonderman, Diane M. Becker, Paul Elliott, Tõnu Esko, Christian Gieger, Hans J. Grabe, Timo A. Lakka, Terho Lehtimäki, Kari E. North, Brenda W.J.H. Penninx, Peter Vollenweider, Lynne E. Wagenknecht, Tangchun Wu, Yong Bing Xiang, Wei Zheng, Donna K. Arnett, Claude Bouchard, Michele K. Evans, Vilmundur Gudnason, Sharon Kardia, Tanika N. Kelly, Stephen B. Kritchevsky, Ruth J.F. Loos, Alexandre C. Pereira, Mike Province, Bruce M. Psaty, Charles Rotimi, Xiaofeng Zhu, Najaf Amin, L. Adrienne Cupples, Myriam Fornage, Ervin F. Fox, Xiuqing Guo, W. James Gauderman, Kenneth Rice, Charles Kooperberg, Patricia B. Munroe, Ching Ti Liu, Alanna C. Morrison, Dabeeru C. Rao, Diana van Heemst, Susan Redline

Epidemiology & Community Health

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.

Original language	English (US)
Article number	5121
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12958-0
State	Published - Dec 1 2019

Bibliographical note

Funding Information:
D.O.M.K. is a part-time research consultant for Metabolon, Inc. H.J.G. has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm and Janssen Cilag. H.J.G. has received research funding from the German Research Foundation (DFG), the German Ministry of Education and Research (BMBF), the DAMP Foundation, Fresenius Medical Care, the EU “Joint Programme Neurodegenerative Disorders (JPND) and the European Social Fund (ESF)”. S.A. reports employment and stock options with 23andMe, Inc.

Funding Information:
This project was supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305). This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Tuomas O. Kilpeläinen was supported by the Danish Council for Independent Research (DFF–6110-00183) and the Novo Nordisk Foundation (NNF18CC0034900, NNF17OC0026848 and NNF15CC0018486). Diana van Heemst was supported by the European Commission funded project HUMAN (Health-2013-INNOVATION-1-602757). Susan Redline was supported in part by NIH R35HL135818 and HL11338. Study-specific acknowledgements can be found in the Supplementary Notes 2 and 4. The data on coronary artery disease have been contributed by the Myocardial Infarction Genetics and CARDIoGRAM investigators, and have been downloaded from www.CARDIOGRAMPLUSC4D.ORG.

Publisher Copyright:
© 2019, The Author(s).

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Noordam, R., Bos, M. M., Wang, H., Winkler, T. W., Bentley, A. R., Kilpeläinen, T. O., de Vries, P. S., Sung, Y. J., Schwander, K., Cade, B. E., Manning, A., Aschard, H., Brown, M. R., Chen, H., Franceschini, N., Musani, S. K., Richard, M., Vojinovic, D., Aslibekyan, S., ... Redline, S. (2019). Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration. Nature communications, 10(1), Article 5121. https://doi.org/10.1038/s41467-019-12958-0

Noordam, R, Bos, MM, Wang, H, Winkler, TW, Bentley, AR, Kilpeläinen, TO, de Vries, PS, Sung, YJ, Schwander, K, Cade, BE, Manning, A, Aschard, H, Brown, MR, Chen, H, Franceschini, N, Musani, SK, Richard, M, Vojinovic, D, Aslibekyan, S, Bartz, TM, de las Fuentes, L, Feitosa, M, Horimoto, AR, Ilkov, M, Kho, M, Kraja, A, Li, C, Lim, E, Liu, Y, Mook-Kanamori, DO, Rankinen, T, Tajuddin, SM, van der Spek, A, Wang, Z, Marten, J, Laville, V, Alver, M, Evangelou, E, Graff, ME, He, M, Kühnel, B, Lyytikäinen, LP, Marques-Vidal, P, Nolte, IM, Palmer, ND, Rauramaa, R, Shu, XO, Snieder, H, Weiss, S, Wen, W, Yanek, LR, Adolfo, C, Ballantyne, C, Bielak, L, Biermasz, NR, Boerwinkle, E, Dimou, N, Eiriksdottir, G, Gao, C, Gharib, SA, Gottlieb, DJ, Haba-Rubio, J, Harris, TB, Heikkinen, S, Heinzer, R, Hixson, JE, Homuth, G, Ikram, MA, Komulainen, P, Krieger, JE, Lee, J, Liu, J, Lohman, KK, Luik, AI, Mägi, R, Martin, LW, Meitinger, T, Metspalu, A, Milaneschi, Y, Nalls, MA, O’Connell, J, Peters, A, Peyser, P, Raitakari, OT, Reiner, AP, Rensen, PCN, Rice, TK, Rich, SS, Roenneberg, T, Rotter, JI, Schreiner, PJ, Shikany, J, Sidney, SS, Sims, M, Sitlani, CM, Sofer, T, Strauch, K, Swertz, MA, Taylor, KD, Uitterlinden, AG, van Duijn, CM, Völzke, H, Waldenberger, M, Wallance, RB, van Dijk, KW, Yu, C, Zonderman, AB, Becker, DM, Elliott, P, Esko, T, Gieger, C, Grabe, HJ, Lakka, TA, Lehtimäki, T, North, KE, Penninx, BWJH, Vollenweider, P, Wagenknecht, LE, Wu, T, Xiang, YB, Zheng, W, Arnett, DK, Bouchard, C, Evans, MK, Gudnason, V, Kardia, S, Kelly, TN, Kritchevsky, SB, Loos, RJF, Pereira, AC, Province, M, Psaty, BM, Rotimi, C, Zhu, X, Amin, N, Cupples, LA, Fornage, M, Fox, EF, Guo, X, Gauderman, WJ, Rice, K, Kooperberg, C, Munroe, PB, Liu, CT, Morrison, AC, Rao, DC, van Heemst, D & Redline, S 2019, 'Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration', Nature communications, vol. 10, no. 1, 5121. https://doi.org/10.1038/s41467-019-12958-0

@article{886baf9aab794246bf76296271fc2ba2,

title = "Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration",

abstract = "Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.",

author = "Raymond Noordam and Bos, {Maxime M.} and Heming Wang and Winkler, {Thomas W.} and Bentley, {Amy R.} and Kilpel{\"a}inen, {Tuomas O.} and {de Vries}, {Paul S.} and Sung, {Yun Ju} and Karen Schwander and Cade, {Brian E.} and Alisa Manning and Hugues Aschard and Brown, {Michael R.} and Han Chen and Nora Franceschini and Musani, {Solomon K.} and Melissa Richard and Dina Vojinovic and Stella Aslibekyan and Bartz, {Traci M.} and {de las Fuentes}, Lisa and Mary Feitosa and Horimoto, {Andrea R.} and Marjan Ilkov and Minjung Kho and Aldi Kraja and Changwei Li and Elise Lim and Yongmei Liu and Mook-Kanamori, {Dennis O.} and Tuomo Rankinen and Tajuddin, {Salman M.} and {van der Spek}, Ashley and Zhe Wang and Jonathan Marten and Vincent Laville and Maris Alver and Evangelos Evangelou and Graff, {Maria E.} and Meian He and Brigitte K{\"u}hnel and Lyytik{\"a}inen, {Leo Pekka} and Pedro Marques-Vidal and Nolte, {Ilja M.} and Palmer, {Nicholette D.} and Rainer Rauramaa and Shu, {Xiao Ou} and Harold Snieder and Stefan Weiss and Wanqing Wen and Yanek, {Lisa R.} and Correa Adolfo and Christie Ballantyne and Larry Bielak and Biermasz, {Nienke R.} and Eric Boerwinkle and Niki Dimou and Gudny Eiriksdottir and Chuan Gao and Gharib, {Sina A.} and Gottlieb, {Daniel J.} and Jos{\'e} Haba-Rubio and Harris, {Tamara B.} and Sami Heikkinen and Rapha{\"e}l Heinzer and Hixson, {James E.} and Georg Homuth and Ikram, {M. Arfan} and Pirjo Komulainen and Krieger, {Jose E.} and Jiwon Lee and Jingmin Liu and Lohman, {Kurt K.} and Luik, {Annemarie I.} and Reedik M{\"a}gi and Martin, {Lisa W.} and Thomas Meitinger and Andres Metspalu and Yuri Milaneschi and Nalls, {Mike A.} and Jeff O{\textquoteright}Connell and Annette Peters and Patricia Peyser and Raitakari, {Olli T.} and Reiner, {Alex P.} and Rensen, {Patrick C.N.} and Rice, {Treva K.} and Rich, {Stephen S.} and Till Roenneberg and Rotter, {Jerome I.} and Schreiner, {Pamela J.} and James Shikany and Sidney, {Stephen S.} and Mario Sims and Sitlani, {Colleen M.} and Tamar Sofer and Konstantin Strauch and Swertz, {Morris A.} and Taylor, {Kent D.} and Uitterlinden, {Andr{\'e} G.} and {van Duijn}, {Cornelia M.} and Henry V{\"o}lzke and Melanie Waldenberger and Wallance, {Robert B.} and {van Dijk}, {Ko Willems} and Caizheng Yu and Zonderman, {Alan B.} and Becker, {Diane M.} and Paul Elliott and T{\~o}nu Esko and Christian Gieger and Grabe, {Hans J.} and Lakka, {Timo A.} and Terho Lehtim{\"a}ki and North, {Kari E.} and Penninx, {Brenda W.J.H.} and Peter Vollenweider and Wagenknecht, {Lynne E.} and Tangchun Wu and Xiang, {Yong Bing} and Wei Zheng and Arnett, {Donna K.} and Claude Bouchard and Evans, {Michele K.} and Vilmundur Gudnason and Sharon Kardia and Kelly, {Tanika N.} and Kritchevsky, {Stephen B.} and Loos, {Ruth J.F.} and Pereira, {Alexandre C.} and Mike Province and Psaty, {Bruce M.} and Charles Rotimi and Xiaofeng Zhu and Najaf Amin and Cupples, {L. Adrienne} and Myriam Fornage and Fox, {Ervin F.} and Xiuqing Guo and Gauderman, {W. James} and Kenneth Rice and Charles Kooperberg and Munroe, {Patricia B.} and Liu, {Ching Ti} and Morrison, {Alanna C.} and Rao, {Dabeeru C.} and {van Heemst}, Diana and Susan Redline",

note = "Funding Information: D.O.M.K. is a part-time research consultant for Metabolon, Inc. H.J.G. has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm and Janssen Cilag. H.J.G. has received research funding from the German Research Foundation (DFG), the German Ministry of Education and Research (BMBF), the DAMP Foundation, Fresenius Medical Care, the EU “Joint Programme Neurodegenerative Disorders (JPND) and the European Social Fund (ESF)”. S.A. reports employment and stock options with 23andMe, Inc. Funding Information: This project was supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305). This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Tuomas O. Kilpel{\"a}inen was supported by the Danish Council for Independent Research (DFF–6110-00183) and the Novo Nordisk Foundation (NNF18CC0034900, NNF17OC0026848 and NNF15CC0018486). Diana van Heemst was supported by the European Commission funded project HUMAN (Health-2013-INNOVATION-1-602757). Susan Redline was supported in part by NIH R35HL135818 and HL11338. Study-specific acknowledgements can be found in the Supplementary Notes 2 and 4. The data on coronary artery disease have been contributed by the Myocardial Infarction Genetics and CARDIoGRAM investigators, and have been downloaded from www.CARDIOGRAMPLUSC4D.ORG. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-12958-0",

language = "English (US)",

volume = "10",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

AU - Noordam, Raymond

AU - Bos, Maxime M.

AU - Wang, Heming

AU - Winkler, Thomas W.

AU - Bentley, Amy R.

AU - Kilpeläinen, Tuomas O.

AU - de Vries, Paul S.

AU - Sung, Yun Ju

AU - Schwander, Karen

AU - Cade, Brian E.

AU - Manning, Alisa

AU - Aschard, Hugues

AU - Brown, Michael R.

AU - Chen, Han

AU - Franceschini, Nora

AU - Musani, Solomon K.

AU - Richard, Melissa

AU - Vojinovic, Dina

AU - Aslibekyan, Stella

AU - Bartz, Traci M.

AU - de las Fuentes, Lisa

AU - Feitosa, Mary

AU - Horimoto, Andrea R.

AU - Ilkov, Marjan

AU - Kho, Minjung

AU - Kraja, Aldi

AU - Li, Changwei

AU - Lim, Elise

AU - Liu, Yongmei

AU - Mook-Kanamori, Dennis O.

AU - Rankinen, Tuomo

AU - Tajuddin, Salman M.

AU - van der Spek, Ashley

AU - Wang, Zhe

AU - Marten, Jonathan

AU - Laville, Vincent

AU - Alver, Maris

AU - Evangelou, Evangelos

AU - Graff, Maria E.

AU - He, Meian

AU - Kühnel, Brigitte

AU - Lyytikäinen, Leo Pekka

AU - Marques-Vidal, Pedro

AU - Nolte, Ilja M.

AU - Palmer, Nicholette D.

AU - Rauramaa, Rainer

AU - Shu, Xiao Ou

AU - Snieder, Harold

AU - Weiss, Stefan

AU - Wen, Wanqing

AU - Yanek, Lisa R.

AU - Adolfo, Correa

AU - Ballantyne, Christie

AU - Bielak, Larry

AU - Biermasz, Nienke R.

AU - Boerwinkle, Eric

AU - Dimou, Niki

AU - Eiriksdottir, Gudny

AU - Gao, Chuan

AU - Gharib, Sina A.

AU - Gottlieb, Daniel J.

AU - Haba-Rubio, José

AU - Harris, Tamara B.

AU - Heikkinen, Sami

AU - Heinzer, Raphaël

AU - Hixson, James E.

AU - Homuth, Georg

AU - Ikram, M. Arfan

AU - Komulainen, Pirjo

AU - Krieger, Jose E.

AU - Lee, Jiwon

AU - Liu, Jingmin

AU - Lohman, Kurt K.

AU - Luik, Annemarie I.

AU - Mägi, Reedik

AU - Martin, Lisa W.

AU - Meitinger, Thomas

AU - Metspalu, Andres

AU - Milaneschi, Yuri

AU - Nalls, Mike A.

AU - O’Connell, Jeff

AU - Peters, Annette

AU - Peyser, Patricia

AU - Raitakari, Olli T.

AU - Reiner, Alex P.

AU - Rensen, Patrick C.N.

AU - Rice, Treva K.

AU - Rich, Stephen S.

AU - Roenneberg, Till

AU - Rotter, Jerome I.

AU - Schreiner, Pamela J.

AU - Shikany, James

AU - Sidney, Stephen S.

AU - Sims, Mario

AU - Sitlani, Colleen M.

AU - Sofer, Tamar

AU - Strauch, Konstantin

AU - Swertz, Morris A.

AU - Taylor, Kent D.

AU - Uitterlinden, André G.

AU - van Duijn, Cornelia M.

AU - Völzke, Henry

AU - Waldenberger, Melanie

AU - Wallance, Robert B.

AU - van Dijk, Ko Willems

AU - Yu, Caizheng

AU - Zonderman, Alan B.

AU - Becker, Diane M.

AU - Elliott, Paul

AU - Esko, Tõnu

AU - Gieger, Christian

AU - Grabe, Hans J.

AU - Lakka, Timo A.

AU - Lehtimäki, Terho

AU - North, Kari E.

AU - Penninx, Brenda W.J.H.

AU - Vollenweider, Peter

AU - Wagenknecht, Lynne E.

AU - Wu, Tangchun

AU - Xiang, Yong Bing

AU - Zheng, Wei

AU - Arnett, Donna K.

AU - Bouchard, Claude

AU - Evans, Michele K.

AU - Gudnason, Vilmundur

AU - Kardia, Sharon

AU - Kelly, Tanika N.

AU - Kritchevsky, Stephen B.

AU - Loos, Ruth J.F.

AU - Pereira, Alexandre C.

AU - Province, Mike

AU - Psaty, Bruce M.

AU - Rotimi, Charles

AU - Zhu, Xiaofeng

AU - Amin, Najaf

AU - Cupples, L. Adrienne

AU - Fornage, Myriam

AU - Fox, Ervin F.

AU - Guo, Xiuqing

AU - Gauderman, W. James

AU - Rice, Kenneth

AU - Kooperberg, Charles

AU - Munroe, Patricia B.

AU - Liu, Ching Ti

AU - Morrison, Alanna C.

AU - Rao, Dabeeru C.

AU - van Heemst, Diana

AU - Redline, Susan

N1 - Funding Information: D.O.M.K. is a part-time research consultant for Metabolon, Inc. H.J.G. has received travel grants and speakers honoraria from Fresenius Medical Care, Neuraxpharm and Janssen Cilag. H.J.G. has received research funding from the German Research Foundation (DFG), the German Ministry of Education and Research (BMBF), the DAMP Foundation, Fresenius Medical Care, the EU “Joint Programme Neurodegenerative Disorders (JPND) and the European Social Fund (ESF)”. S.A. reports employment and stock options with 23andMe, Inc. Funding Information: This project was supported by a grant from the US National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (R01HL118305). This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. Tuomas O. Kilpeläinen was supported by the Danish Council for Independent Research (DFF–6110-00183) and the Novo Nordisk Foundation (NNF18CC0034900, NNF17OC0026848 and NNF15CC0018486). Diana van Heemst was supported by the European Commission funded project HUMAN (Health-2013-INNOVATION-1-602757). Susan Redline was supported in part by NIH R35HL135818 and HL11338. Study-specific acknowledgements can be found in the Supplementary Notes 2 and 4. The data on coronary artery disease have been contributed by the Myocardial Infarction Genetics and CARDIoGRAM investigators, and have been downloaded from www.CARDIOGRAMPLUSC4D.ORG. Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.

AB - Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.

UR - http://www.scopus.com/inward/record.url?scp=85074934485&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074934485&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-12958-0

DO - 10.1038/s41467-019-12958-0

M3 - Article

C2 - 31719535

AN - SCOPUS:85074934485

SN - 2041-1723

VL - 10

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 5121

ER -

Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

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