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2. Multi-trait analysis of genome-wide association summary statistics using MTAG

Author

Turley, Patrick, Walters, Raymond K, Maghzian, Omeed, Okbay, Aysu, Lee, James J, Fontana, Mark Alan, Nguyen-Viet, Tuan Anh, Wedow, Robbee, Zacher, Meghan, Furlotte, Nicholas A, 23andMe Research Team, Social Science Genetic Association Consortium, Magnusson, Patrik, Oskarsson, Sven, Johannesson, Magnus, Visscher, Peter M, Laibson, David, Cesarini, David, Neale, Benjamin M, and Benjamin, Daniel J

Subjects
Biological Sciences, Genetics, Human Genome, Algorithms, Data Interpretation, Statistical, Datasets as Topic, Depression, Diagnostic Self Evaluation, Genetic Association Studies, Genome-Wide Association Study, Health, Humans, Meta-Analysis as Topic, Multifactorial Inheritance, Neuroticism, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, 23andMe Research Team, Social Science Genetic Association Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

We introduce multi-trait analysis of GWAS (MTAG), a method for joint analysis of summary statistics from genome-wide association studies (GWAS) of different traits, possibly from overlapping samples. We apply MTAG to summary statistics for depressive symptoms (N eff = 354,862), neuroticism (N = 168,105), and subjective well-being (N = 388,538). As compared to the 32, 9, and 13 genome-wide significant loci identified in the single-trait GWAS (most of which are themselves novel), MTAG increases the number of associated loci to 64, 37, and 49, respectively. Moreover, association statistics from MTAG yield more informative bioinformatics analyses and increase the variance explained by polygenic scores by approximately 25%, matching theoretical expectations.

Published
2018

3. Author Correction: Multi-trait analysis of genome-wide association summary statistics using MTAG

Author

Turley, Patrick, Walters, Raymond K., Maghzian, Omeed, Okbay, Aysu, Lee, James J., Fontana, Mark Alan, Nguyen-Viet, Tuan Anh, Wedow, Robbee, Zacher, Meghan, Furlotte, Nicholas A., 23andMe Research Team, Social Science Genetic Association Consortium, Magnusson, Patrik, Oskarsson, Sven, Johannesson, Magnus, Visscher, Peter M., Laibson, David, Cesarini, David, Neale, Benjamin M., and Benjamin, Daniel J.

Published
2019
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4. Publisher Correction: Multi-trait analysis of genome-wide association summary statistics using MTAG

Author

Turley, Patrick, Walters, Raymond K., Maghzian, Omeed, Okbay, Aysu, Lee, James J., Fontana, Mark Alan, Nguyen-Viet, Tuan Anh, Wedow, Robbee, Zacher, Meghan, Furlotte, Nicholas A., 23andMe Research Team, Social Science Genetic Association Consortium, Magnusson, Patrik, Oskarsson, Sven, Johannesson, Magnus, Visscher, Peter M., Laibson, David, Cesarini, David, Neale, Benjamin M., and Benjamin, Daniel J.

Published
2019
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5. Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals

Author

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, and Cappuccio, Francesco

Subjects
0301 basic medicine, Male, Netherlands Twin Register (NTR), Multifactorial Inheritance, genetic association, LOCI, Medizin, Genome-wide association study, INTELLIGENCE, Cohort Studies, 0302 clinical medicine, GWAS, Genetics, Aged, 80 and over, Genome, HERITABILITY, HUMAN TRAITS, Middle Aged, HUMAN BRAIN, STATISTICS, 3. Good health, Phenotype, Meta-analysis, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], educational attainment, POPULATIONS, Educational Status, Female, genome-wide-significant SNPs, SDG 4 - Quality Education, Adult, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, SNP, Humans, QH426, Behavioural genetics, METAANALYSIS, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Sequence Analysis, DNA, Heritability, Educational attainment, polygenic prediction, 030104 developmental biology, Genome-Wide Association Study, MAPPING CAUSAL VARIANTS, 030217 neurology & neurosurgery
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.

Published
2018

7. GWAS of educational attainment, phase 3: prediction

Author

Wedow, Robbee, Okbay, Aysu, Kong, Edward, Turley, Patrick, Lee, James, Zacher, Meghan, Thom, Kevin, Anh Tuan Nguyen, Maghzian, Omeed, Linner, Richard Karlsson, Robinson, Matthew, Peter Visscher, Cesarini, David, and Benjamin, Daniel

8. GWAS of educational attainment: phase 3-main results

Author

Okbay, Aysu, Wedow, Robbee, Kong, Edward, Turley, Patrick, Lee, James, Zacher, Meghan, Thom, Kevin, Anh Tuan Nguyen, Maghzian, Omeed, Linner, Richard Karlsson, Robinson, Matthew, Peter Visscher, Benjamin, Daniel, and Cesarini, David

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

Author

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, Li, Hui, Li, Ruoxi, Royer, Rebecca, Timshel, Pascal N, Walters, Raymond K, Willoughby, Emily A, Yengo, Loïc, 23andMe Research Team, COGENT (Cognitive Genomics Consortium), Social Science Genetic Association Consortium, Alver, Maris, Bao, Yanchun, Clark, David W, Day, Felix R, Furlotte, Nicholas A, Joshi, Peter K, Kemper, Kathryn E, Kleinman, Aaron, Langenberg, Claudia, Mägi, Reedik, Trampush, Joey W, Verma, Shefali Setia, Wu, Yang, Lam, Max, Zhao, Jing Hua, Zheng, Zhili, Boardman, Jason D, Campbell, Harry, Freese, Jeremy, Harris, Kathleen Mullan, Hayward, Caroline, Herd, Pamela, Kumari, Meena, Lencz, Todd, Luan, Jian'an, Malhotra, Anil K, Metspalu, Andres, Milani, Lili, Ong, Ken K, Perry, John RB, Porteous, David J, Ritchie, Marylyn D, Smart, Melissa C, Smith, Blair H, Tung, Joyce Y, Wareham, Nicholas J, Wilson, James F, Beauchamp, Jonathan P, Conley, Dalton C, Esko, Tõnu, Lehrer, Steven F, Magnusson, Patrik KE, Oskarsson, Sven, Pers, Tune H, Robinson, Matthew R, Thom, Kevin, Watson, Chelsea, Chabris, Christopher F, Meyer, Michelle N, Laibson, David I, Yang, Jian, Johannesson, Magnus, Koellinger, Philipp D, Turley, Patrick, Visscher, Peter M, Benjamin, Daniel J, and Cesarini, David

Subjects
Adult, Aged, 80 and over, Male, Multifactorial Inheritance, Middle Aged, Polymorphism, Single Nucleotide, 3. Good health, Cohort Studies, Phenotype, Educational Status, Humans, Female, Aged, Genome-Wide Association Study
Abstract

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., Medical Research Council (MC_UU_12015/1), Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135), MRC (MC_PC_13048), Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)

10. GWAS of educational attainment, phase 3: biological findings

Author

Lee, James, Okbay, Aysu, Wedow, Robbee, Kong, Edward, Turley, Patrick, Zacher, Meghan, Thom, Kevin, Anh Tuan Nguyen Viet, Maghzian, Omeed, Linner, Richard Karlsson, Robinson, Matthew, Peter Visscher, Benjamin, Daniel, and Cesarini, David

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

Author

Lee JJ, Wedow R, Okbay A, Kong E, Maghzian O, Zacher M, Nguyen-Viet TA, Bowers P, Sidorenko J, Karlsson Linnér R, Fontana MA, Kundu T, Lee C, Li H, Li R, Royer R, Timshel PN, Walters RK, Willoughby EA, Yengo L, Alver M, Bao Y, Clark DW, Day FR, Furlotte NA, Joshi PK, Kemper KE, Kleinman A, Langenberg C, Mägi R, Trampush JW, Verma SS, Wu Y, Lam M, Zhao JH, Zheng Z, Boardman JD, Campbell H, Freese J, Harris KM, Hayward C, Herd P, Kumari M, Lencz T, Luan J, Malhotra AK, Metspalu A, Milani L, Ong KK, Perry JRB, Porteous DJ, Ritchie MD, Smart MC, Smith BH, Tung JY, Wareham NJ, Wilson JF, Beauchamp JP, Conley DC, Esko T, Lehrer SF, Magnusson PKE, Oskarsson S, Pers TH, Robinson MR, Thom K, Watson C, Chabris CF, Meyer MN, Laibson DI, Yang J, Johannesson M, Koellinger PD, Turley P, Visscher PM, Benjamin DJ, and Cesarini D

Subjects
Adult, Aged, Aged, 80 and over, Cohort Studies, Educational Status, Female, Genome-Wide Association Study methods, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Multifactorial Inheritance
Abstract

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.

Published
2018
Full Text
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