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

Patrick Turley; Raymond K. Walters; Omeed Maghzian; Aysu Okbay; James J. Lee; Mark Alan Fontana; Tuan Anh Nguyen-Viet; Robbee Wedow; Meghan Zacher; Nicholas A. Furlotte; Patrik Magnusson; Sven Oskarsson; Magnus Johannesson; Peter M. Visscher; David Laibson; David Cesarini; Benjamin M. Neale; Daniel J. Benjamin; Michelle Agee; Babak Alipanahi; Adam Auton; Robert K. Bell; Katarzyna Bryc; Sarah L. Elson; Pierre Fontanillas; David A. Hinds; Bethann S. Hromatka; Karen E. Huber; Aaron Kleinman; Nadia K. Litterman; Matthew H. McIntyre; Joanna L. Mountain; Carrie A.M. Northover; J. Fah Sathirapongsasuti; Olga V. Sazonova; Janie F. Shelton; Suyash Shringarpure; Chao Tian; Joyce Y. Tung; Vladimir Vacic; Catherine H. Wilson; Steven J. Pitts

doi:10.1038/s41588-017-0009-4

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

Patrick Turley, Raymond K. Walters, Omeed Maghzian, Aysu Okbay, James J. Lee, Mark Alan Fontana, Tuan Anh Nguyen-Viet, Robbee Wedow, Meghan Zacher, Nicholas A. Furlotte, Patrik Magnusson, Sven Oskarsson, Magnus Johannesson, Peter M. Visscher, David Laibson, David Cesarini, Benjamin M. Neale, Daniel J. Benjamin, Michelle Agee, Babak AlipanahiAdam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, David A. Hinds, Bethann S. Hromatka, Karen E. Huber, Aaron Kleinman, Nadia K. Litterman, Matthew H. McIntyre, Joanna L. Mountain, Carrie A.M. Northover, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Joyce Y. Tung, Vladimir Vacic, Catherine H. Wilson, Steven J. Pitts

Research output: Contribution to journal › Article

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.

Original language	English (US)
Pages (from-to)	229-237
Number of pages	9
Journal	Nature Genetics
Volume	50
Issue number	2
DOIs	https://doi.org/10.1038/s41588-017-0009-4
State	Published - Feb 1 2018

ASJC Scopus subject areas

Genetics

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Turley, P., Walters, R. K., Maghzian, O., Okbay, A., Lee, J. J., Fontana, M. A., Nguyen-Viet, T. A., Wedow, R., Zacher, M., Furlotte, N. A., Magnusson, P., Oskarsson, S., Johannesson, M., Visscher, P. M., Laibson, D., Cesarini, D., Neale, B. M., Benjamin, D. J., Agee, M., ... Pitts, S. J. (2018). Multi-trait analysis of genome-wide association summary statistics using MTAG. Nature Genetics, 50(2), 229-237. https://doi.org/10.1038/s41588-017-0009-4

Multi-trait analysis of genome-wide association summary statistics using MTAG. / 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.; Magnusson, Patrik; Oskarsson, Sven; Johannesson, Magnus; Visscher, Peter M.; Laibson, David; Cesarini, David; Neale, Benjamin M.; Benjamin, Daniel J.; Agee, Michelle; Alipanahi, Babak; Auton, Adam; Bell, Robert K.; Bryc, Katarzyna; Elson, Sarah L.; Fontanillas, Pierre; Hinds, David A.; Hromatka, Bethann S.; Huber, Karen E.; Kleinman, Aaron; Litterman, Nadia K.; McIntyre, Matthew H.; Mountain, Joanna L.; Northover, Carrie A.M.; Sathirapongsasuti, J. Fah; Sazonova, Olga V.; Shelton, Janie F.; Shringarpure, Suyash; Tian, Chao; Tung, Joyce Y.; Vacic, Vladimir; Wilson, Catherine H.; Pitts, Steven J.

In: Nature Genetics, Vol. 50, No. 2, 01.02.2018, p. 229-237.

Research output: Contribution to journal › Article

Turley, P, Walters, RK, Maghzian, O, Okbay, A, Lee, JJ, Fontana, MA, Nguyen-Viet, TA, Wedow, R, Zacher, M, Furlotte, NA, Magnusson, P, Oskarsson, S, Johannesson, M, Visscher, PM, Laibson, D, Cesarini, D, Neale, BM, Benjamin, DJ, Agee, M, Alipanahi, B, Auton, A, Bell, RK, Bryc, K, Elson, SL, Fontanillas, P, Hinds, DA, Hromatka, BS, Huber, KE, Kleinman, A, Litterman, NK, McIntyre, MH, Mountain, JL, Northover, CAM, Sathirapongsasuti, JF, Sazonova, OV, Shelton, JF, Shringarpure, S, Tian, C, Tung, JY, Vacic, V, Wilson, CH & Pitts, SJ 2018, 'Multi-trait analysis of genome-wide association summary statistics using MTAG', Nature Genetics, vol. 50, no. 2, pp. 229-237. https://doi.org/10.1038/s41588-017-0009-4

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. ; Magnusson, Patrik ; Oskarsson, Sven ; Johannesson, Magnus ; Visscher, Peter M. ; Laibson, David ; Cesarini, David ; Neale, Benjamin M. ; Benjamin, Daniel J. ; Agee, Michelle ; Alipanahi, Babak ; Auton, Adam ; Bell, Robert K. ; Bryc, Katarzyna ; Elson, Sarah L. ; Fontanillas, Pierre ; Hinds, David A. ; Hromatka, Bethann S. ; Huber, Karen E. ; Kleinman, Aaron ; Litterman, Nadia K. ; McIntyre, Matthew H. ; Mountain, Joanna L. ; Northover, Carrie A.M. ; Sathirapongsasuti, J. Fah ; Sazonova, Olga V. ; Shelton, Janie F. ; Shringarpure, Suyash ; Tian, Chao ; Tung, Joyce Y. ; Vacic, Vladimir ; Wilson, Catherine H. ; Pitts, Steven J. / Multi-trait analysis of genome-wide association summary statistics using MTAG. In: Nature Genetics. 2018 ; Vol. 50, No. 2. pp. 229-237.

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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.",

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AU - Fontana, Mark Alan

AU - Nguyen-Viet, Tuan Anh

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AU - Shelton, Janie F.

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