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Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals

Authors :
Lee, James J.
Wedow, Robbee
Okbay, Aysu
Kong, Edward
Maghzian, Omeed
Zacher, Meghan
Nguyen-Viet, Tuan Anh
Bowers, Peter
Sidorenko, Julia
Karlsson Linnér, Richard
Fontana, Mark Alan
Kundu, Tushar
Lee, Chanwook
Hui, Li
Ruoxi, Li
Royer, Rebecca
Timshel, Pascal N.
Walters, Raymond K.
Willoughby, Emily A.
Yengo, Loïc
Agee, Michelle
Alipanahi, Babak
Auton, Adam
Bell, Robert K.
Bryc, Katarzyna
Elson, Sarah L.
Fontanillas, Pierre
Hinds, David A.
Mccreight, Jennifer C.
Huber, Karen E.
Litterman, Nadia K.
Mcintyre, Matthew H.
Mountain, Joanna L.
Noblin, Elizabeth S.
Northover, Carrie A. M.
Pitts, Steven J.
Sathirapongsasuti, J. Fah
Sazonova, Olga V.
Shelton, Janie F.
Shringarpure, Suyash
Tian, Chao
Vacic, Vladimir
Wilson, Catherine H.
Beauchamp, Jonathan P.
Pers, Tune H.
Rietveld, Cornelius A.
Turley, Patrick
Chen, Guo-Bo
Emilsson, Valur
Meddens, S. Fleur W.
Oskarsson, Sven
Pickrell, Joseph K.
Thom, Kevin
Timshel, Pascal
Vlaming, Ronald de
Abdellaoui, Abdel
Ahluwalia, Tarunveer S.
Bacelis, Jonas
Baumbach, Clemens
Bjornsdottir, Gyda
Brandsma, Johannes H.
Concas, Maria Pina
Derringer, Jaime
Furlotte, Nicholas A.
Galesloot, Tessel E.
Girotto, Giorgia
Gupta, Richa
Hall, Leanne M.
Harris, Sarah E.
Hofer, Edith
Horikoshi, Momoko
Huffman, Jennifer E.
Kaasik, Kadri
Kalafati, Ioanna P.
Karlsson, Robert
Kong, Augustine
Lahti, Jari
van der Lee, Sven J.
Leeuw, Christiaan de
Lind, Penelope A.
Lindgren, Karl-Oskar
Liu, Tian
Mangino, Massimo
Marten, Jonathan
Mihailov, Evelin
Miller, Michael B.
van der Most, Peter J.
Oldmeadow, Christopher
Payton, Antony
Pervjakova, Natalia
Peyrot, Wouter J.
Qian, Yong
Raitakari, Olli
Rueedi, Rico
Salvi, Erika
Schmidt, Börge
Schraut, Katharina E.
Shi, Jianxin
Smith, Albert V.
Poot, Raymond A.
St Pourcain, Beate
Teumer, Alexander
Thorleifsson, Gudmar
Verweij, Niek
Vuckovic, Dragana
Wellmann, Juergen
Westra, Harm-Jan
Yang, Jingyun
Zhao, Wei
Zhu, Zhihong
Alizadeh, Behrooz Z.
Amin, Najaf
Bakshi, Andrew
Baumeister, Sebastian E.
Biino, Ginevra
Bønnelykke, Klaus
Boyle, Patricia A.
Campbell, Harry
Cappuccio, Francesco P.
Davies, Gail
De Neve, Jan-Emmanuel
Deloukas, Panos
Demuth, Ilja
Ding, Jun
Eibich, Peter
Eisele, Lewin
Eklund, Niina
Evans, David M.
Faul, Jessica D.
Feitosa, Mary F.
Forstner, Andreas J.
Gandin, Ilaria
Gunnarsson, Bjarni
Halldórsson, Bjarni V.
Harris, Tamara B.
Heath, Andrew C.
Hocking, Lynne J.
Holliday, Elizabeth G.
Homuth, Georg
Horan, Michael A.
Hottenga, Jouke-Jan
de Jager, Philip L.
Joshi, Peter K.
Jugessur, Astanand
Kaakinen, Marika A.
Kähönen, Mika
Kanoni, Stavroula
Keltigangas-Järvinen, Liisa
Kiemeney, Lambertus A. L. M.
Kolcic, Ivana
Koskinen, Seppo
Kraja, Aldi T.
Kroh, Martin
Kutalik, Zoltan
Latvala, Antti
Launer, Lenore J.
Lebreton, Maël P.
Levinson, Douglas F.
Lichtenstein, Paul
Lichtner, Peter
Liewald, David C. M.
Loukola
LifeLines Cohort Study
Anu
Madden, Pamela A.
Mägi, Reedik
Mäki-Opas, Tomi
Marioni, Riccardo E.
Marques-Vidal, Pedro
Meddens, Gerardus A.
Mcmahon, George
Meisinger, Christa
Meitinger, Thomas
Milaneschi, Yusplitri
Milani, Lili
Montgomery, Grant W.
Myhre, Ronny
Nelson, Christopher P.
Nyholt, Dale R.
Ollier, William E. R.
Palotie, Aarno
Paternoster, Lavinia
Pedersen, Nancy L.
Petrovic, Katja E.
Porteous, David J.
Räikkönen, Katri
Ring, Susan M.
Robino, Antonietta
Rostapshova, Olga
Rudan, Igor
Rustichini, Aldo
Salomaa, Veikko
Sanders, Alan R.
Sarin, Antti-Pekka
Schmidt, Helena
Scott, Rodney J.
Smith, Blair H.
Smith, Jennifer A.
Staessen, Jan A.
Steinhagen-Thiessen, Elisabeth
Strauch, Konstantin
Terracciano, Antonio
Tobin, Martin D.
Ulivi, Sheila
Vaccargiu, Simona
Quaye, Lydia
van Rooij, Frank J. A.
Venturini, Cristina
Vinkhuyzen, Anna A. E.
Völker, Uwe
Völzke, Henry
Vonk, Judith M.
Vozzi, Diego
Waage, Johannes
Ware, Erin B.
Willemsen, Gonneke
Attia, John R.
Bennett, David A.
Berger, Klaus
Bertram, Lars
Bisgaard, Hans
Boomsma, Dorret I.
Borecki, Ingrid B.
Bültmann, Ute
Chabris, Christopher F.
Cucca, Francesco
Cusi, Daniele
Deary, Ian J.
Dedoussis, George V.
van Duijn, Cornelia M.
Eriksson, Johan G.
Franke, Barbara
Franke, Lude
Gasparini, Paolo
Gejman, Pablo V.
Gieger, Christian
Grabe, Hans-Jörgen
Gratten, Jacob
Groenen, Patrick J. F.
Gudnason, Vilmundur
van der Harst, Pim
Hayward, Caroline
Hoffmann, Wolfgang
Hyppönen, Elina
Iacono, William G.
Jacobsson, Bo
Järvelin, Marjo-Riitta
Jöckel, Karl-Heinz
Kaprio, Jaakko
Kardia, Sharon L. R.
Lehtimäki, Terho
Lehrer, Steven F.
Magnusson, Patrik K. E.
Martin, Nicholas G.
Mcgue, Matt
Metspalu, Andres
Pendleton, Neil
Penninx, Brenda W. J. H.
Perola, Markus
Pirastu, Nicola
Pirastu, Mario
Polasek, Ozren
Posthuma, Danielle
Power, Christine
Province, Michael A.
Samani, Nilesh J.
Schlessinger, David
Schmidt, Reinhold
Sørensen, Thorkild I. A.
Spector, Tim D.
Stefansson, Kari
Thorsteinsdottir, Unnur
Thurik, A. Roy
Timpson, Nicholas J.
Tiemeier, Henning
Tung, Joyce Y.
Uitterlinden, André G.
Vitart, Veronique
Vollenweider, Peter
Weir, David R.
Wilson, James F.
Wright, Alan F.
Conley, Dalton C.
Krueger, Robert F.
Smith, George Davey
Hofman, Albert
Laibson, David I.
Medland, Sarah E.
Meyer, Michelle N.
Yang, Jian
Johannesson, Magnus
Visscher, Peter M.
Esko, Tõnu
Koellinger, Philipp D.
Cesarini, David
Benjamin, Daniel J.
Alver, Maris
Bao, Yanchun
Clark, David W.
Day, Felix R.
Kemper, Kathryn E.
Kleinman, Aaron
Langenberg, Claudia
Trampush, Joey W.
Verma, Shefali Setia
Yang, Wu
Lam, Max
Zhao, Jing Hua
Zheng, Zhili
Boardman, Jason D.
Freese, Jeremy
Harris, Kathleen Mullan
Herd, Pamela
Kumari, Meena
Lencz, Todd
Luan, Jian’An
Malhotra, Anil K.
Ong, Ken K.
Perry, John R. B.
Ritchie, Marylyn D.
Smart, Melissa C.
Wareham, Nicholas J.
Robinson, Matthew R.
Watson, Chelsea
Lee, James J
Wedow, Robbee
Okbay, Aysu
Kong, Edward
Hyppönen, Elina
Cesarini, David
23andMe Research Team
COGENT (Cognitive Genomics Consortium)
Social Science Genetic Association Consortium
LifeLines Cohort Study
Economics
Amsterdam Neuroscience - Complex Trait Genetics
Biological Psychology
APH - Personalized Medicine
APH - Health Behaviors & Chronic Diseases
Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep
APH - Mental Health
APH - Methodology
Complex Trait Genetics
Lee, James J.
Maghzian, Omeed
Zacher, Meghan
Nguyen-Viet, Tuan Anh
Bowers, Peter
Sidorenko, Julia
Karlsson Linnér, Richard
Fontana, Mark Alan
Kundu, Tushar
Lee, Chanwook
Li, Hui
Li, Ruoxi
Royer, Rebecca
Timshel, Pascal N.
Walters, Raymond K.
Willoughby, Emily A.
Yengo, Loïc
Agee, Michelle
Alipanahi, Babak
Auton, Adam
Bell, Robert K.
Bryc, Katarzyna
Elson, Sarah L.
Fontanillas, Pierre
Hinds, David A.
Mccreight, Jennifer C.
Huber, Karen E.
Litterman, Nadia K.
Mcintyre, Matthew H.
Mountain, Joanna L.
Noblin, Elizabeth S.
Northover, Carrie A. M.
Pitts, Steven J.
Sathirapongsasuti, J. Fah
Sazonova, Olga V.
Shelton, Janie F.
Shringarpure, Suyash
Tian, Chao
Vacic, Vladimir
Wilson, Catherine H.
Beauchamp, Jonathan P.
Pers, Tune H.
Rietveld, Cornelius A.
Turley, Patrick
Chen, Guo-Bo
Emilsson, Valur
Meddens, S. Fleur W.
Oskarsson, Sven
Pickrell, Joseph K.
Thom, Kevin
Timshel, Pascal
Vlaming, Ronald de
Abdellaoui, Abdel
Ahluwalia, Tarunveer S.
Bacelis, Jona
Baumbach, Clemen
Bjornsdottir, Gyda
Brandsma, Johannes H.
Concas, Maria Pina
Derringer, Jaime
Furlotte, Nicholas A.
Galesloot, Tessel E.
Girotto, Giorgia
Gupta, Richa
Hall, Leanne M.
Harris, Sarah E.
Hofer, Edith
Horikoshi, Momoko
Huffman, Jennifer E.
Kaasik, Kadri
Kalafati, Ioanna P.
Karlsson, Robert
Kong, Augustine
Lahti, Jari
van der Lee, Sven J.
Leeuw, Christiaan de
Lind, Penelope A.
Lindgren, Karl-Oskar
Liu, Tian
Mangino, Massimo
Marten, Jonathan
Mihailov, Evelin
Miller, Michael B.
van der Most, Peter J.
Oldmeadow, Christopher
Payton, Antony
Pervjakova, Natalia
Peyrot, Wouter J.
Qian, Yong
Raitakari, Olli
Rueedi, Rico
Salvi, Erika
Schmidt, Börge
Schraut, Katharina E.
Shi, Jianxin
Smith, Albert V.
Poot, Raymond A.
St Pourcain, Beate
Teumer, Alexander
Thorleifsson, Gudmar
Verweij, Niek
Vuckovic, Dragana
Wellmann, Juergen
Westra, Harm-Jan
Yang, Jingyun
Zhao, Wei
Zhu, Zhihong
Alizadeh, Behrooz Z.
Amin, Najaf
Bakshi, Andrew
Baumeister, Sebastian E.
Biino, Ginevra
Bønnelykke, Klau
Boyle, Patricia A.
Campbell, Harry
Cappuccio, Francesco P.
Davies, Gail
De Neve, Jan-Emmanuel
Deloukas, Pano
Demuth, Ilja
Ding, Jun
Eibich, Peter
Eisele, Lewin
Eklund, Niina
Evans, David M.
Faul, Jessica D.
Feitosa, Mary F.
Forstner, Andreas J.
Gandin, Ilaria
Gunnarsson, Bjarni
Halldórsson, Bjarni V.
Harris, Tamara B.
Heath, Andrew C.
Hocking, Lynne J.
Holliday, Elizabeth G.
Homuth, Georg
Horan, Michael A.
Hottenga, Jouke-Jan
de Jager, Philip L.
Joshi, Peter K.
Jugessur, Astanand
Kaakinen, Marika A.
Kähönen, Mika
Kanoni, Stavroula
Keltigangas-Järvinen, Liisa
Kiemeney, Lambertus A. L. M.
Kolcic, Ivana
Koskinen, Seppo
Kraja, Aldi T.
Kroh, Martin
Kutalik, Zoltan
Latvala, Antti
Launer, Lenore J.
Lebreton, Maël P.
Levinson, Douglas F.
Lichtenstein, Paul
Lichtner, Peter
Liewald, David C. M.
Loukola
LifeLines Cohort, Study
Anu
Madden, Pamela A.
Mägi, Reedik
Mäki-Opas, Tomi
Marioni, Riccardo E.
Marques-Vidal, Pedro
Meddens, Gerardus A.
Mcmahon, George
Meisinger, Christa
Meitinger, Thoma
Milaneschi, Yusplitri
Milani, Lili
Montgomery, Grant W.
Myhre, Ronny
Nelson, Christopher P.
Nyholt, Dale R.
Ollier, William E. R.
Palotie, Aarno
Paternoster, Lavinia
Pedersen, Nancy L.
Petrovic, Katja E.
Porteous, David J.
Räikkönen, Katri
Ring, Susan M.
Robino, Antonietta
Rostapshova, Olga
Rudan, Igor
Rustichini, Aldo
Salomaa, Veikko
Sanders, Alan R.
Sarin, Antti-Pekka
Schmidt, Helena
Scott, Rodney J.
Smith, Blair H.
Smith, Jennifer A.
Staessen, Jan A.
Steinhagen-Thiessen, Elisabeth
Strauch, Konstantin
Terracciano, Antonio
Tobin, Martin D.
Ulivi, Sheila
Vaccargiu, Simona
Quaye, Lydia
van Rooij, Frank J. A.
Venturini, Cristina
Vinkhuyzen, Anna A. E.
Völker, Uwe
Völzke, Henry
Vonk, Judith M.
Vozzi, Diego
Waage, Johanne
Ware, Erin B.
Willemsen, Gonneke
Attia, John R.
Bennett, David A.
Berger, Klau
Bertram, Lar
Bisgaard, Han
Boomsma, Dorret I.
Borecki, Ingrid B.
Bültmann, Ute
Chabris, Christopher F.
Cucca, Francesco
Cusi, Daniele
Deary, Ian J.
Dedoussis, George V.
van Duijn, Cornelia M.
Eriksson, Johan G.
Franke, Barbara
Franke, Lude
Gasparini, Paolo
Gejman, Pablo V.
Gieger, Christian
Grabe, Hans-Jörgen
Gratten, Jacob
Groenen, Patrick J. F.
Gudnason, Vilmundur
van der Harst, Pim
Hayward, Caroline
Hoffmann, Wolfgang
Iacono, William G.
Jacobsson, Bo
Järvelin, Marjo-Riitta
Jöckel, Karl-Heinz
Kaprio, Jaakko
Kardia, Sharon L. R.
Lehtimäki, Terho
Lehrer, Steven F.
Magnusson, Patrik K. E.
Martin, Nicholas G.
Mcgue, Matt
Metspalu, Andre
Pendleton, Neil
Penninx, Brenda W. J. H.
Perola, Marku
Pirastu, Nicola
Pirastu, Mario
Polasek, Ozren
Posthuma, Danielle
Power, Christine
Province, Michael A.
Samani, Nilesh J.
Schlessinger, David
Schmidt, Reinhold
Sørensen, Thorkild I. A.
Spector, Tim D.
Stefansson, Kari
Thorsteinsdottir, Unnur
Thurik, A. Roy
Timpson, Nicholas J.
Tiemeier, Henning
Tung, Joyce Y.
Uitterlinden, André G.
Vitart, Veronique
Vollenweider, Peter
Weir, David R.
Wilson, James F.
Wright, Alan F.
Conley, Dalton C.
Krueger, Robert F.
Smith, George Davey
Hofman, Albert
Laibson, David I.
Medland, Sarah E.
Meyer, Michelle N.
Yang, Jian
Johannesson, Magnu
Visscher, Peter M.
Esko, Tõnu
Koellinger, Philipp D.
Benjamin, Daniel J.
Alver, Mari
Bao, Yanchun
Clark, David W.
Day, Felix R.
Kemper, Kathryn E.
Kleinman, Aaron
Langenberg, Claudia
Trampush, Joey W.
Verma, Shefali Setia
Wu, Yang
Lam, Max
Zhao, Jing Hua
Zheng, Zhili
Boardman, Jason D.
Freese, Jeremy
Harris, Kathleen Mullan
Herd, Pamela
Kumari, Meena
Lencz, Todd
Luan, Jian’An
Malhotra, Anil K.
Ong, Ken K.
Perry, John R. B.
Ritchie, Marylyn D.
Smart, Melissa C.
Wareham, Nicholas J.
Robinson, Matthew R.
Watson, Chelsea
Faculteit Medische Wetenschappen/UMCG
Life Course Epidemiology (LCE)
Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Groningen Research Institute for Asthma and COPD (GRIAC)
Department of Health and Life Sciences
Public Health Research (PHR)
Stem Cell Aging Leukemia and Lymphoma (SALL)
Cardiovascular Centre (CVC)
Neurology
Psychiatry
Human genetics
Amsterdam Reproduction & Development (AR&D)
APH - Digital Health
Medical Oncology
Applied Economics
Day, Felix [0000-0003-3789-7651]
Langenberg, Claudia [0000-0002-5017-7344]
Zhao, Jing Hua [0000-0003-4930-3582]
Luan, Jian'an [0000-0003-3137-6337]
Ong, Kenneth [0000-0003-4689-7530]
Perry, John [0000-0001-6483-3771]
Wareham, Nicholas [0000-0003-1422-2993]
Apollo - University of Cambridge Repository
Cappuccio, Francesco
Source :
Nat. Genet. 52, 1112-1121 (2018), Nature Genetics, Nature Genetics, 50(8), 1112-1121. Nature Publishing Group, 23Andme Research Team, Abdellaoui, A, Peyrot, W J, Hottenga, J J, Vinkhuyzen, A A E, Willemsen, G, Boomsma, D I, van Duijn, C M, Penninx, B, Posthuma, D & Uitterlinden, A G 2018, ' Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals ', Nature Genetics, vol. 50, no. 8, pp. 1112-1121 . https://doi.org/10.1038/s41588-018-0147-3, Nature Genetics, 50, 1112-1121, 2018, ' Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals ', Nature Genetics, vol. 50, no. 8, pp. 1112-+ . https://doi.org/10.1038/s41588-018-0147-3, Nature genetics, 50(8), 1112-1121. Nature Publishing Group, Nature Genetics, 50, 8, pp. 1112-1121, Nature Genetics, 50(8), 1112-+. Nature Publishing Group, 23andMe Research team 2018, ' Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals ', Nature Genetics, vol. 50, no. 8, pp. 1112-1121 . https://doi.org/10.1038/s41588-018-0147-3, 23andMe Research Team & Pendleton, N 2018, ' Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals ', Nature Genetics, vol. 50, no. 8, pp. 1112-1121 . https://doi.org/10.1038/s41588-018-0147-3
Publication Year :
2018
Publisher :
Nature Publishing Group, 2018.

Abstract

Contains fulltext : 195595.pdf (Publisher’s version ) (Open Access) Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.

Details

ISSN :
10614036
Database :
OpenAIRE
Journal :
Nat. Genet. 52, 1112-1121 (2018), Nature Genetics, Nature Genetics, 50(8), 1112-1121. Nature Publishing Group, 23Andme Research Team, Abdellaoui, A, Peyrot, W J, Hottenga, J J, Vinkhuyzen, A A E, Willemsen, G, Boomsma, D I, van Duijn, C M, Penninx, B, Posthuma, D & Uitterlinden, A G 2018, ' Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals ', Nature Genetics, vol. 50, no. 8, pp. 1112-1121 . https://doi.org/10.1038/s41588-018-0147-3, Nature Genetics, 50, 1112-1121, 2018, ' Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals ', Nature Genetics, vol. 50, no. 8, pp. 1112-+ . https://doi.org/10.1038/s41588-018-0147-3, Nature genetics, 50(8), 1112-1121. Nature Publishing Group, Nature Genetics, 50, 8, pp. 1112-1121, Nature Genetics, 50(8), 1112-+. Nature Publishing Group, 23andMe Research team 2018, ' Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals ', Nature Genetics, vol. 50, no. 8, pp. 1112-1121 . https://doi.org/10.1038/s41588-018-0147-3, 23andMe Research Team & Pendleton, N 2018, ' Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals ', Nature Genetics, vol. 50, no. 8, pp. 1112-1121 . https://doi.org/10.1038/s41588-018-0147-3
Accession number :
edsair.doi.dedup.....8d23aa9d89404a0315f7a0c671918a03