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35. Ambient Pollution Exposureand Sleep Quality in Spiromics

Author

Koch, A.L., primary, Putcha, N., additional, Woo, H., additional, Paulin, L.M., additional, Barr, R.G., additional, Comellas, A.P., additional, Cooper, C.B., additional, Barjaktarevic, I., additional, Zeidler, M.R., additional, Billings, M.E., additional, Bowler, R.P., additional, Baugh, A.D., additional, Han, M.K., additional, Kim, V., additional, Paine, R., additional, Dransfield, M.T., additional, Krishnan, J.A., additional, Peters, S.P., additional, Punjabi, N.M., additional, Woodruff, P., additional, Kaufman, J.D., additional, and Hansel, N.N., additional

Published
2020
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43. Lower Oxygen Saturation During Sleep Is Associated with Reduced Expressions of CD1D and RAB20 That Is Potentially Reversed by CPAP Therapy

Author

Li, R., primary, Joehanes, R., additional, Lin, H., additional, Gower, A., additional, Cade, B.E., additional, Li, J., additional, Williams, S., additional, Wang, H., additional, Punjabi, N.M., additional, Mehra, R., additional, Patel, S.R., additional, Quan, S.F., additional, Liu, Y., additional, Gharib, S.A., additional, Rotter, J., additional, Rich, S., additional, Levy, D., additional, Spira, A., additional, Redline, S.S., additional, Gottlieb, D.J., additional, and Sofer, T., additional

Published
2019
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45. Metabolomic Analysis of Obstructive Sleep Apnea Traits

Author

Ngo, D., primary, Peterson, B., additional, Montanez, R., additional, Sofer, T., additional, Morningstar, J., additional, Shi, X., additional, Gottlieb, D.J., additional, Lewis, E., additional, Mehra, R., additional, Patel, S.R., additional, Punjabi, N.M., additional, Quan, S.F., additional, Gerszten, R., additional, and Redline, S.S., additional

Published
2019
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46. Control of confounding and reporting of results in causal inference studies.

Author

Adjei A.A., Branson R.D., Chalmers J.D., Marshall R., Maslove D.M., Ost D.E., Punjabi N.M., Schatz M., Smyth A.R., Stewart P.W., Suissa S., Akdis C.A., Azoulay E., Bakker J., Ballas Z.K., Bardin P.G., Barreiro E., Bellomo R., Bernstein J.A., Brusasco V., Buchman T.G., Chokroverty S., Collop N.A., Crapo J.D., Fitzgerald D.A., Hale L., Hart N., Herth F.J., Iwashyna T.J., Jenkins G., Kolb M., Marks G.B., Mazzone P., Moorman J.R., Murphy T.M., Noah T.L., Reynolds P., Riemann D., Russell R.E., Sheikh A., Sotgiu G., Swenson E.R., Szczesniak R., Szymusiak R., Teboul J.-L., Vincent J.-L., Lederer D.J., Bell S.C., Adjei A.A., Branson R.D., Chalmers J.D., Marshall R., Maslove D.M., Ost D.E., Punjabi N.M., Schatz M., Smyth A.R., Stewart P.W., Suissa S., Akdis C.A., Azoulay E., Bakker J., Ballas Z.K., Bardin P.G., Barreiro E., Bellomo R., Bernstein J.A., Brusasco V., Buchman T.G., Chokroverty S., Collop N.A., Crapo J.D., Fitzgerald D.A., Hale L., Hart N., Herth F.J., Iwashyna T.J., Jenkins G., Kolb M., Marks G.B., Mazzone P., Moorman J.R., Murphy T.M., Noah T.L., Reynolds P., Riemann D., Russell R.E., Sheikh A., Sotgiu G., Swenson E.R., Szczesniak R., Szymusiak R., Teboul J.-L., Vincent J.-L., Lederer D.J., and Bell S.C.

Published
2019

47. Genetic variants in RBFOX3 are associated with sleep latency

Author

Amin, N., Allebrandt, K.V., Spek, A. van der, Muller-Myhsok, B., Hek, K., Teder-Laving, M., Hayward, C., Esko, T., Mill, J.G. van, Mbarek, H., Watson, N.F., Melville, S.A., Del Greco, F.M., Byrne, E.M., Oole, E., Kolcic, I., Chen, T., Evans, D.S., Coresh, J., Vogelzangs, N., Karjalainen, J., Willemsen, G., Gharib, S.A., Zgaga, L., Mihailov, E., Stone, K.L., Campbell, H., Brouwer, R.W.W., Demirkan, A., Isaacs, A., Dogas, Z., Marciante, K.D., Campbell, S., Borovecki, F., Luik, A.I., Li, M., Hottenga, J.J., Huffman, J.E., Hout, M.C.G.N. van den, Cummings, S.R., Aulchenko, Y.S., Gehrman, P.R., Uitterlinden, A.G., Wichmann, H.E., Muller-Nurasyid, M., Fehrmann, R.S.N., Montgomery, G.W., Hofman, A., Kao, W.H.L., Oostra, B.A., Wright, A.F., Vink, J.M., Wilson, J.F., Pramstaller, P.P., Hicks, A.A., Polasek, O., Punjabi, N.M., Redline, S., Psaty, B.M., Heath, A.C., Merrow, M., Tranah, G.J., Gottlieb, D.J., Boomsma, D.I., Martin, N.G., Rudan, I., Tiemeier, H., IJcken, W.F.J. van, Penninx, B.W.J.H., Metspalu, A., Meitinger, T., Franke, L., Roenneberg, T., Duijn, C.M. van, Amin, N., Allebrandt, K.V., Spek, A. van der, Muller-Myhsok, B., Hek, K., Teder-Laving, M., Hayward, C., Esko, T., Mill, J.G. van, Mbarek, H., Watson, N.F., Melville, S.A., Del Greco, F.M., Byrne, E.M., Oole, E., Kolcic, I., Chen, T., Evans, D.S., Coresh, J., Vogelzangs, N., Karjalainen, J., Willemsen, G., Gharib, S.A., Zgaga, L., Mihailov, E., Stone, K.L., Campbell, H., Brouwer, R.W.W., Demirkan, A., Isaacs, A., Dogas, Z., Marciante, K.D., Campbell, S., Borovecki, F., Luik, A.I., Li, M., Hottenga, J.J., Huffman, J.E., Hout, M.C.G.N. van den, Cummings, S.R., Aulchenko, Y.S., Gehrman, P.R., Uitterlinden, A.G., Wichmann, H.E., Muller-Nurasyid, M., Fehrmann, R.S.N., Montgomery, G.W., Hofman, A., Kao, W.H.L., Oostra, B.A., Wright, A.F., Vink, J.M., Wilson, J.F., Pramstaller, P.P., Hicks, A.A., Polasek, O., Punjabi, N.M., Redline, S., Psaty, B.M., Heath, A.C., Merrow, M., Tranah, G.J., Gottlieb, D.J., Boomsma, D.I., Martin, N.G., Rudan, I., Tiemeier, H., IJcken, W.F.J. van, Penninx, B.W.J.H., Metspalu, A., Meitinger, T., Franke, L., Roenneberg, T., and Duijn, C.M. van

Abstract

Item does not contain fulltext, 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 x 10-08, 6.59 x 10-08 and 9.17 x 10-08). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 x 10-02, 7.0 x 10-03 and 2.5 x 10-03; combined meta-analysis P-values=5.5 x 10-07, 5.4 × 10-07 and 1.0 x 10-07). A functional prediction of RBFOX3 based on co-expression with other genes shows that this gene is predominantly expressed in brain (P-value=1.4 x 10-316) and the central nervous system (P-value=7.5 x 10-321). The predicted function of RBFOX3 based on co-expression analysis with other genes shows that this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines (P-values<2.9 x 10-11) that are crucial in triggering the onset of sleep. To conclude, in this first large-scale GWAS of sleep latency we report a novel association of variants in RBFOX3 gene. Further, a functional prediction of RBFOX3 supports the involvement of RBFOX3 with sleep latency.

Published
2016

48. 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
Full Text
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49. Novel loci associated with usual sleep duration: The CHARGE Consortium Genome-Wide Association Study

Author

Gottlieb, D.J., Hek, K., Chen, T.H., Watson, N.F., Eiriksdottir, G., Byrne, E.M., Cornelis, M., Warby, S.C., Bandinelli, S., Cherkas, L., Evans, D.S., Grabe, H.J., Lahti, J., Li, M., Lehtimaki, T., Lumley, T., Marciante, K.D., Pérusse, L., Psaty, B.M., Robbins, J., Tranah, G.J., Vink, J.M., Wilk, J.B., Stafford, J.M., Bellis, C., Biffar, R., Bouchard, C., Cade, B., Curhan, G.C., Eriksson, J.G., Ewert, R., Ferrucci, L., Fulop, T., Gehrman, P.R., Goodloe, R., Harris, T.B., Heath, A.C., Hernandez, D.G., Hofman, A., Hottenga, J.J., Hunter, D.J., Jensen, M.K., Johnson, A.D., Kahonen, M., Kao, L., Kraft, P., Larkin, E.K., Lauderdale, D.S., Luik, A.I., Medici, M., Montgomery, G.W., Palotie, A., Patel, S.R., Pistis, G., Porcu, E., Quaye, L., Raitakari, O., Redline, S., Rimm, E.B., Rotter, J.I., Smith, A.V., Spector, T.D., Teumer, A., Uitterlinden, A.G., Vohl, M.C., Widen, E., Willemsen, G., Young, T., Zhang, X., Liu, Y., Blangero, J., Boomsma, D.I., Gudnason, V., Hu, F., Mangino, M., Martin, N.G., O'Connor, G.T., Stone, K.L., Tanaka, T., Viikari, J., Gharib, S.A., Punjabi, N.M., Raikkonen, K., Völzke, H., Mignot, E., Tiemeier, H., Gottlieb, D.J., Hek, K., Chen, T.H., Watson, N.F., Eiriksdottir, G., Byrne, E.M., Cornelis, M., Warby, S.C., Bandinelli, S., Cherkas, L., Evans, D.S., Grabe, H.J., Lahti, J., Li, M., Lehtimaki, T., Lumley, T., Marciante, K.D., Pérusse, L., Psaty, B.M., Robbins, J., Tranah, G.J., Vink, J.M., Wilk, J.B., Stafford, J.M., Bellis, C., Biffar, R., Bouchard, C., Cade, B., Curhan, G.C., Eriksson, J.G., Ewert, R., Ferrucci, L., Fulop, T., Gehrman, P.R., Goodloe, R., Harris, T.B., Heath, A.C., Hernandez, D.G., Hofman, A., Hottenga, J.J., Hunter, D.J., Jensen, M.K., Johnson, A.D., Kahonen, M., Kao, L., Kraft, P., Larkin, E.K., Lauderdale, D.S., Luik, A.I., Medici, M., Montgomery, G.W., Palotie, A., Patel, S.R., Pistis, G., Porcu, E., Quaye, L., Raitakari, O., Redline, S., Rimm, E.B., Rotter, J.I., Smith, A.V., Spector, T.D., Teumer, A., Uitterlinden, A.G., Vohl, M.C., Widen, E., Willemsen, G., Young, T., Zhang, X., Liu, Y., Blangero, J., Boomsma, D.I., Gudnason, V., Hu, F., Mangino, M., Martin, N.G., O'Connor, G.T., Stone, K.L., Tanaka, T., Viikari, J., Gharib, S.A., Punjabi, N.M., Raikkonen, K., Völzke, H., Mignot, E., and Tiemeier, H.

Abstract

Contains fulltext : 160002.pdf (publisher's version ) (Closed access), 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[thinsp]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 [times] 10-9). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 [times] 10-4). The strongest combined association was at rs1823125 (P=1.5 [times] 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[thinsp]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

50. 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
Full Text
View/download PDF

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