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

Author

Noordam, R. (Raymond), Bos, M.M. (Maxime M.), Wang, H. (Heming), Winkler, T.W. (Thomas W.), Bentley, A.R. (Amy), Kilpeläinen, T.O. (Tuomas O.), Vries, P.S. (Paul) de, Sung, Y.J. (Yun Ju), Schwander, K., Cade, B., Manning, A.K. (Alisa), Aschard, H. (Hugues), Brown, M.R., Chen, H. (Han), Franceschini, N. (Nora), Musani, S.K. (Solomon K.), Richard, M. (Melissa), Vojinović, D. (Dina), Aslibekyan, S. (Stella), Bartz, T.M. (Traci M.), de Las Fuentes, L. (Lisa), Feitosa, M.F. (Mary Furlan), Horimoto, A.R. (Andrea R.), Ilkov, M. (Marjan), Kho, M. (Minjung), Kraja, A. (Aldi), Li, C. (Changwei), Lim, E. (Elise), Liu, Y. (YongMei), Mook-Kanamori, D.O. (Dennis O.), Rankinen, T. (Tuomo), Tajuddin, S.M. (Salman M.), Spek, A. (Ashley) van der, Wang, Z. (Zhe), Marten, J. (Jonathan), Laville, V. (Vincent), Alver, M. (Maris), Evangelou, E. (Evangelos), Graff, M.E. (Maria E.), He, M. (Meian), Kuhnel, B. (Brigitte), Lyytikäinen, L.-P. (Leo-Pekka), Marques-Vidal, P. (Pedro), Nolte, I.M. (Ilja), Palmer, N.D. (Nicholette), Rauramaa, R. (Rainer), Shu, X.-O. (Xiao-Ou), Snieder, H. (Harold), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Adolfo, C. (Correa), Ballantyne, C. (Christie), Bielak, L.F. (Lawrence F.), Biermasz, N.R., Boerwinkle, E.A. (Eric), Dimou, N. (Niki), Eiriksdottir, G. (Gudny), Gao, C. (Chuan), Gharib, S.A. (Sina), Gottlieb, D.J. (Daniel J.), Haba-Rubio, J. (José), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heinzer, R. (Raphaël), Hixson, J.E. (James E.), Homuth, G. (Georg), Ikram, M.A. (Arfan), Komulainen, P. (Pirjo), Krieger, J.E. (José), Lee, J. (Jiwon), Liu, J. (Jingmin), Lohman, K.K. (Kurt K.), Luik, A.I. (Annemarie), Mägi, R. (Reedik), Martin, L.W. (Lisa), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Nalls, M.A. (Michael), O´Connell, J.R., Peters, A. (Annette), Peyser, P.A. (Patricia A.), Raitakari, O. (Olli), Reiner, A. (Alexander), Rensen, P.C.N. (Patrick), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Roenneberg, T., Rotter, J.I. (Jerome I.), Schreiner, P.J. (Pamela), Shikany, J. (James), Sidney, S.S. (Stephen S.), Sims, M. (Mario), Sitlani, C.M. (Colleen M.), Sofer, T. (Tamar), Strauch, K. (Konstantin), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Völzke, H. (Henry), Waldenberger, M. (Melanie), Wallance, R.B. (Robert B.), van Dijk, K.W. (Ko Willems), Yu, C. (Caizheng), Zonderman, A.B. (Alan B.), Becker, D.M. (Diane), Elliott, P. (Paul), Esko, T. (Tõnu), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), North, K.E. (Kari), Penninx, B.W.J.H. (Brenda), Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wu, T. (Tangchun), Xiang, Y.-B. (Yong-Bing), Zheng, W. (Wei), Arnett, D.K. (Donna), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Kardia, S.L.R. (Sharon), Kelly, T.N. (Tanika N.), Kritchevsky, S.B. (Stephen), Loos, R.J.F. (Ruth), Pereira, A. (A.), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rotimi, C. (Charles), Zhu, X. (Xiaofeng), Amin, N. (Najaf), Cupples, L.A. (L Adrienne), Fornage, M. (Myriam), Fox, E.F. (Ervin F.), Guo, X. (Xiuqing), Gauderman, W.J. (W James), Rice, K.M. (Kenneth), Kooperberg, C. (Charles), Munroe, P. (Patricia), Liu, C.-T. (Ching-Ti), Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), Heemst, D. (Diana) van, Redline, S. (Susan), Noordam, R. (Raymond), Bos, M.M. (Maxime M.), Wang, H. (Heming), Winkler, T.W. (Thomas W.), Bentley, A.R. (Amy), Kilpeläinen, T.O. (Tuomas O.), Vries, P.S. (Paul) de, Sung, Y.J. (Yun Ju), Schwander, K., Cade, B., Manning, A.K. (Alisa), Aschard, H. (Hugues), Brown, M.R., Chen, H. (Han), Franceschini, N. (Nora), Musani, S.K. (Solomon K.), Richard, M. (Melissa), Vojinović, D. (Dina), Aslibekyan, S. (Stella), Bartz, T.M. (Traci M.), de Las Fuentes, L. (Lisa), Feitosa, M.F. (Mary Furlan), Horimoto, A.R. (Andrea R.), Ilkov, M. (Marjan), Kho, M. (Minjung), Kraja, A. (Aldi), Li, C. (Changwei), Lim, E. (Elise), Liu, Y. (YongMei), Mook-Kanamori, D.O. (Dennis O.), Rankinen, T. (Tuomo), Tajuddin, S.M. (Salman M.), Spek, A. (Ashley) van der, Wang, Z. (Zhe), Marten, J. (Jonathan), Laville, V. (Vincent), Alver, M. (Maris), Evangelou, E. (Evangelos), Graff, M.E. (Maria E.), He, M. (Meian), Kuhnel, B. (Brigitte), Lyytikäinen, L.-P. (Leo-Pekka), Marques-Vidal, P. (Pedro), Nolte, I.M. (Ilja), Palmer, N.D. (Nicholette), Rauramaa, R. (Rainer), Shu, X.-O. (Xiao-Ou), Snieder, H. (Harold), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Adolfo, C. (Correa), Ballantyne, C. (Christie), Bielak, L.F. (Lawrence F.), Biermasz, N.R., Boerwinkle, E.A. (Eric), Dimou, N. (Niki), Eiriksdottir, G. (Gudny), Gao, C. (Chuan), Gharib, S.A. (Sina), Gottlieb, D.J. (Daniel J.), Haba-Rubio, J. (José), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heinzer, R. (Raphaël), Hixson, J.E. (James E.), Homuth, G. (Georg), Ikram, M.A. (Arfan), Komulainen, P. (Pirjo), Krieger, J.E. (José), Lee, J. (Jiwon), Liu, J. (Jingmin), Lohman, K.K. (Kurt K.), Luik, A.I. (Annemarie), Mägi, R. (Reedik), Martin, L.W. (Lisa), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Nalls, M.A. (Michael), O´Connell, J.R., Peters, A. (Annette), Peyser, P.A. (Patricia A.), Raitakari, O. (Olli), Reiner, A. (Alexander), Rensen, P.C.N. (Patrick), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Roenneberg, T., Rotter, J.I. (Jerome I.), Schreiner, P.J. (Pamela), Shikany, J. (James), Sidney, S.S. (Stephen S.), Sims, M. (Mario), Sitlani, C.M. (Colleen M.), Sofer, T. (Tamar), Strauch, K. (Konstantin), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Völzke, H. (Henry), Waldenberger, M. (Melanie), Wallance, R.B. (Robert B.), van Dijk, K.W. (Ko Willems), Yu, C. (Caizheng), Zonderman, A.B. (Alan B.), Becker, D.M. (Diane), Elliott, P. (Paul), Esko, T. (Tõnu), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), North, K.E. (Kari), Penninx, B.W.J.H. (Brenda), Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wu, T. (Tangchun), Xiang, Y.-B. (Yong-Bing), Zheng, W. (Wei), Arnett, D.K. (Donna), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Kardia, S.L.R. (Sharon), Kelly, T.N. (Tanika N.), Kritchevsky, S.B. (Stephen), Loos, R.J.F. (Ruth), Pereira, A. (A.), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rotimi, C. (Charles), Zhu, X. (Xiaofeng), Amin, N. (Najaf), Cupples, L.A. (L Adrienne), Fornage, M. (Myriam), Fox, E.F. (Ervin F.), Guo, X. (Xiuqing), Gauderman, W.J. (W James), Rice, K.M. (Kenneth), Kooperberg, C. (Charles), Munroe, P. (Patricia), Liu, C.-T. (Ching-Ti), Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), Heemst, D. (Diana) van, and Redline, S. (Susan)

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.

Published
2019
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2. Exome-wide meta-analysis identifies rare 3'-UTR variant in ERCC1/CD3EAP associated with symptoms of sleep apnea

Author

Spek, A. (Ashley) van der, Luik, A.I. (Annemarie), Kocevska, D. (Desana), Liu, C. (Chunyu), Brouwer, R.W.W. (Rutger), Rooij, J.G.J. (Jeroen) van, van den hout, M.C.G.N. (Mirjam), Kraaij, R. (Robert), Hofman, A. (Albert), Uitterlinden, A.G. (André), IJcken, W.F.J. (Wilfred) van, Gottlieb, D.J. (Daniel J.), Tiemeier, H.W. (Henning), Duijn, C.M. (Cornelia) van, Amin, N. (Najaf), Spek, A. (Ashley) van der, Luik, A.I. (Annemarie), Kocevska, D. (Desana), Liu, C. (Chunyu), Brouwer, R.W.W. (Rutger), Rooij, J.G.J. (Jeroen) van, van den hout, M.C.G.N. (Mirjam), Kraaij, R. (Robert), Hofman, A. (Albert), Uitterlinden, A.G. (André), IJcken, W.F.J. (Wilfred) van, Gottlieb, D.J. (Daniel J.), Tiemeier, H.W. (Henning), Duijn, C.M. (Cornelia) van, and Amin, N. (Najaf)

Abstract

Obstructive sleep apnea (OSA) is a common sleep breathing disorder associated with an increased risk of cardiovascular and cerebrovascular diseases and mortality. Although OSA is fairly heritable (~40%), there have been only few studies looking into the genetics of OSA. In the present study, we aimed to identify genetic variants associated with symptoms of sleep apnea by performing a whole-exome sequence meta-analysis of symptoms of sleep apnea in 1,475 individuals of European descent. We identified 17 rare genetic variants with at least suggestive evidence of significance. Replication in an independent dataset confirmed the association of a rare genetic variant (rs2229918; minor allele frequency = 0.3%) with symptoms of sleep apnea (p-valuemeta = 6.98 × 10-9, ßmeta = 0.99). Rs2229918 overlaps with the 3' untranslated regions of ERCC1 and CD3EAP genes on chromosome 19q13. Both genes are expressed in tissues in the neck area, such as the tongue, muscles, cartilage and the trachea. Further, CD3EAP is localized in the nucleus and mitochondria and involved in the tumor necrosis factor-alpha/nuclear factor kappa B signaling pathway. Our results and biological functions of CD3EAP/ERCC1 genes suggest that the 19q13 locus is interesting for further OSA research.

Published
2017
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3. Genetic variants in RBFOX3 are associated with sleep latency

Author

Amin, N. (Najaf), Allebrandt, K.V., Spek, A. (Ashley) van der, Müller-Myhsok, B. (B.), Hek, K. (Karin), Teder-Laving, M. (Maris), Hayward, C. (Caroline), Esko, T. (Tõnu), Mill, J. van, Mbarek, H., Watson, N.F. (Nathaniel F), Melville, S.A. (Scott), Del Greco, F.M. (Fabiola), Byrne, E.M. (Enda), Oole, E. (Edwin), Kolcic, I. (Ivana), Chen, T.H., Evans, D.S. (Daniel), Coresh, J. (Josef), Vogelzangs, N. (Nicole), Karjalainen, J. (Juha), Willemsen, G.A.H.M. (Gonneke), Gharib, S.A. (Sina), Zgaga, L. (Lina), Mihailov, E. (Evelin), Stone, K.L. (Katie L), Campbell, H. (Harry), Brouwer, R.W.W. (Rutger), Demirkan, A. (Ayşe), Isaacs, A.J. (Aaron), Dogas, Z., Marciante, K. (Kristin), Campbell, S. (Susan), Borovecki, F. (Fran), Luik, A.I. (Annemarie), Li, M. (Man), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer), van den hout, M.C.G.N. (Mirjam), Cummings, S.R. (Steven R.), Aulchenko, Y.S. (Yurii), Gehrman, P.R. (Philip), Uitterlinden, A.G. (André), Wichmann, H.E. (Heinz Erich), Müller-Nurasyid, M. (Martina), Fehrmann, R.S.N. (Rudolf), Montgomery, G.W. (Grant), Hofman, A. (Albert), Kao, W.H.L. (Wen Hong Linda), Oostra, B.A. (Ben), Wright, A. (Alan), Vink, J.M. (Jacqueline), Wilson, J.F. (James F), Pramstaller, P.P. (Peter Paul), Hicks, A.A. (Andrew), Polasek, O. (Ozren), Punjabi, N.M. (Naresh), Redline, S. (Susan), Psaty, B.M. (Bruce), Heath, A.C. (Andrew C.), Merrow, M., Tranah, G.J. (Gregory), Gottlieb, D.J. (Daniel J), Boomsma, D.I. (Dorret), Martin, N.G. (Nicholas), Rudan, I. (Igor), Tiemeier, H.W. (Henning), IJcken, W.F.J. (Wilfred) van, Penninx, B.W.J.H., Metspalu, A. (Andres), Meitinger, T. (Thomas), Franke, L. (Lude), Roenneberg, T., Duijn, C.M. (Cornelia) van, Amin, N. (Najaf), Allebrandt, K.V., Spek, A. (Ashley) van der, Müller-Myhsok, B. (B.), Hek, K. (Karin), Teder-Laving, M. (Maris), Hayward, C. (Caroline), Esko, T. (Tõnu), Mill, J. van, Mbarek, H., Watson, N.F. (Nathaniel F), Melville, S.A. (Scott), Del Greco, F.M. (Fabiola), Byrne, E.M. (Enda), Oole, E. (Edwin), Kolcic, I. (Ivana), Chen, T.H., Evans, D.S. (Daniel), Coresh, J. (Josef), Vogelzangs, N. (Nicole), Karjalainen, J. (Juha), Willemsen, G.A.H.M. (Gonneke), Gharib, S.A. (Sina), Zgaga, L. (Lina), Mihailov, E. (Evelin), Stone, K.L. (Katie L), Campbell, H. (Harry), Brouwer, R.W.W. (Rutger), Demirkan, A. (Ayşe), Isaacs, A.J. (Aaron), Dogas, Z., Marciante, K. (Kristin), Campbell, S. (Susan), Borovecki, F. (Fran), Luik, A.I. (Annemarie), Li, M. (Man), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer), van den hout, M.C.G.N. (Mirjam), Cummings, S.R. (Steven R.), Aulchenko, Y.S. (Yurii), Gehrman, P.R. (Philip), Uitterlinden, A.G. (André), Wichmann, H.E. (Heinz Erich), Müller-Nurasyid, M. (Martina), Fehrmann, R.S.N. (Rudolf), Montgomery, G.W. (Grant), Hofman, A. (Albert), Kao, W.H.L. (Wen Hong Linda), Oostra, B.A. (Ben), Wright, A. (Alan), Vink, J.M. (Jacqueline), Wilson, J.F. (James F), Pramstaller, P.P. (Peter Paul), Hicks, A.A. (Andrew), Polasek, O. (Ozren), Punjabi, N.M. (Naresh), Redline, S. (Susan), Psaty, B.M. (Bruce), Heath, A.C. (Andrew C.), Merrow, M., Tranah, G.J. (Gregory), Gottlieb, D.J. (Daniel J), Boomsma, D.I. (Dorret), Martin, N.G. (Nicholas), Rudan, I. (Igor), Tiemeier, H.W. (Henning), IJcken, W.F.J. (Wilfred) van, Penninx, B.W.J.H., Metspalu, A. (Andres), Meitinger, T. (Thomas), Franke, L. (Lude), Roenneberg, T., and Duijn, C.M. (Cornelia) van

Abstract

Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We performed a meta-analysis of genome-wide association studies (GWAS) including 2 572 737 single nucleotide polymorphisms (SNPs) established in seven European cohorts including 4242 individuals. We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency (P-values=5.77 × 10-08, 6.59 × 10- 08 and 9.17 × 10- 08). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 × 10- 02, 7.0 × 10- 03 and 2.5 × 10- 03; combined meta-analysis P-values=5.5 × 10-07, 5.4 × 10-07 and 1.0 × 10-07). A functional prediction of RBFOX3 based

Published
2016
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4. Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study

Author

Gottlieb, D.J. (Daniel J), Hek, K. (Karin), Chen, T.-H., Watson, N.F., Eiriksdottir, G. (Gudny), Byrne, E.M., Cornelis, M. (Marilyn), Warby, S.C., Bandinelli, S., Cherkas, L. (Lynn), Evans, D.S. (Daniel), Grabe, H.J. (Hans Jörgen), Lahti, J. (Jari), Li, M. (Man), Lehtimäki, T. (Terho), Lumley, T. (Thomas), Marciante, K. (Kristin), Perusse, L. (Louis), Psaty, B.M. (Bruce), Robbins, J., Tranah, G.J. (Gregory), Vink, J.M., Wilk, J.B., Stafford, J.M., Bellis, C. (Claire), Biffar, R., Bouchard, C. (Claude), Cade, B., Curhan, G.C. (Gary), Eriksson, J., Ewert, R., Ferrucci, L. (Luigi), Fülöp, T., Gehrman, P.R. (Philip), Goodloe, R. (Robert), Harris, T.B. (Tamara), Heath, A.C. (Andrew C.), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Hunter, D. (David), Jensen, M.K. (Majken K.), Johnson, A.D. (Andrew), Kähönen, M. (Mika), Kao, W.H.L. (Wen), Kraft, P. (Peter), Larkin, E.K., Lauderdale, D.S., Luik, A.I. (Annemarie), Medici, M., Montgomery, G.W. (Grant W.), Palotie, A., Patel, S.R. (Sanjay), Pistis, G. (Giorgio), Porcu, E., Quaye, L. (Lydia), Raitakari, O. (Olli), Redline, S. (Susan), Rimm, E.B. (Eric B.), Rotter, J.I., Smith, A.V. (Albert), Spector, T.D. (Timothy), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Vohl, M.-C. (Marie-Claude), Widen, E., Willemsen, G.A.H.M. (Gonneke), Young, T.L. (Terri L.), Zhang, X., Liu, Y., Blangero, J. (John), Boomsma, D.I. (Dorret), Gudnason, V. (Vilmundur), Hu, F., Mangino, M., Martin, N.G. (Nicholas), O'Connor, G.T. (George), Stone, K.L. (Katie L), Tanaka, T., Viikari, J. (Jorma), Gharib, S.A. (Sina), Punjabi, N.M. (Naresh), Räikkönen, K. (Katri), Völzke, H. (Henry), Mignot, E., Tiemeier, H.W. (Henning), Gottlieb, D.J. (Daniel J), Hek, K. (Karin), Chen, T.-H., Watson, N.F., Eiriksdottir, G. (Gudny), Byrne, E.M., Cornelis, M. (Marilyn), Warby, S.C., Bandinelli, S., Cherkas, L. (Lynn), Evans, D.S. (Daniel), Grabe, H.J. (Hans Jörgen), Lahti, J. (Jari), Li, M. (Man), Lehtimäki, T. (Terho), Lumley, T. (Thomas), Marciante, K. (Kristin), Perusse, L. (Louis), Psaty, B.M. (Bruce), Robbins, J., Tranah, G.J. (Gregory), Vink, J.M., Wilk, J.B., Stafford, J.M., Bellis, C. (Claire), Biffar, R., Bouchard, C. (Claude), Cade, B., Curhan, G.C. (Gary), Eriksson, J., Ewert, R., Ferrucci, L. (Luigi), Fülöp, T., Gehrman, P.R. (Philip), Goodloe, R. (Robert), Harris, T.B. (Tamara), Heath, A.C. (Andrew C.), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Hunter, D. (David), Jensen, M.K. (Majken K.), Johnson, A.D. (Andrew), Kähönen, M. (Mika), Kao, W.H.L. (Wen), Kraft, P. (Peter), Larkin, E.K., Lauderdale, D.S., Luik, A.I. (Annemarie), Medici, M., Montgomery, G.W. (Grant W.), Palotie, A., Patel, S.R. (Sanjay), Pistis, G. (Giorgio), Porcu, E., Quaye, L. (Lydia), Raitakari, O. (Olli), Redline, S. (Susan), Rimm, E.B. (Eric B.), Rotter, J.I., Smith, A.V. (Albert), Spector, T.D. (Timothy), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Vohl, M.-C. (Marie-Claude), Widen, E., Willemsen, G.A.H.M. (Gonneke), Young, T.L. (Terri L.), Zhang, X., Liu, Y., Blangero, J. (John), Boomsma, D.I. (Dorret), Gudnason, V. (Vilmundur), Hu, F., Mangino, M., Martin, N.G. (Nicholas), O'Connor, G.T. (George), Stone, K.L. (Katie L), Tanaka, T., Viikari, J. (Jorma), Gharib, S.A. (Sina), Punjabi, N.M. (Naresh), Räikkönen, K. (Katri), Völzke, H. (Henry), Mignot, E., and Tiemeier, H.W. (Henning)

Abstract

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10 -9). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10 -4). The strongest combined association was at rs1823125 (P=1.5 × 10 -10, minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Published
2015
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5. Gene-environment interactions of circadian-related genes for cardiometabolic traits

Author

Dashti, H.S. (Hassan S.), Follis, J.L. (Jack ), Smith, C.E. (Caren), Tanaka, T. (Toshiko), Garaulet, M. (Marta), Gottlieb, D.J. (Daniel J.), Hruby, A. (Adela), Jacques, P.F. (Paul F.), Kiefte-de Jong, J.C. (Jessica), Lamon-Fava, S. (Stefania), Scheer, F.A.J.L. (Frank A.J.L.), Bartz, T.M. (Traci M.), Kovanen, L. (Leena), Wojczynski, M.K. (Mary ), Frazier-Wood, A.C. (Alexis C.), Ahluwalia, T.S. (Tarunveer Singh), Perälä, M.-M. (Mia-Maria), Jonsson, A. (Anna), Muka, T. (Taulant), Kalafati, I.-P. (Ioanna-Panagiota), Mikkilä, V. (Vera), Ordovas, J.M. (Jose), Dashti, H.S. (Hassan S.), Follis, J.L. (Jack ), Smith, C.E. (Caren), Tanaka, T. (Toshiko), Garaulet, M. (Marta), Gottlieb, D.J. (Daniel J.), Hruby, A. (Adela), Jacques, P.F. (Paul F.), Kiefte-de Jong, J.C. (Jessica), Lamon-Fava, S. (Stefania), Scheer, F.A.J.L. (Frank A.J.L.), Bartz, T.M. (Traci M.), Kovanen, L. (Leena), Wojczynski, M.K. (Mary ), Frazier-Wood, A.C. (Alexis C.), Ahluwalia, T.S. (Tarunveer Singh), Perälä, M.-M. (Mia-Maria), Jonsson, A. (Anna), Muka, T. (Taulant), Kalafati, I.-P. (Ioanna-Panagiota), Mikkilä, V. (Vera), and Ordovas, J.M. (Jose)

Published
2015
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