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 › peer-review

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

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

@article{d5ed025cbde0446dbf15deef03233706,

title = "Multi-trait analysis of genome-wide association summary statistics using MTAG",

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.",

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

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doi = "10.1038/s41588-017-0009-4",

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AU - Turley, Patrick

AU - Walters, Raymond K.

AU - Maghzian, Omeed

AU - Okbay, Aysu

AU - Lee, James J.

AU - Fontana, Mark Alan

AU - Nguyen-Viet, Tuan Anh

AU - Wedow, Robbee

AU - Zacher, Meghan

AU - Furlotte, Nicholas A.

AU - Magnusson, Patrik

AU - Oskarsson, Sven

AU - Johannesson, Magnus

AU - Visscher, Peter M.

AU - Laibson, David

AU - Cesarini, David

AU - Neale, Benjamin M.

AU - Benjamin, Daniel J.

AU - Agee, Michelle

AU - Alipanahi, Babak

AU - Auton, Adam

AU - Bell, Robert K.

AU - Bryc, Katarzyna

AU - Elson, Sarah L.

AU - Fontanillas, Pierre

AU - Hinds, David A.

AU - Hromatka, Bethann S.

AU - Huber, Karen E.

AU - Kleinman, Aaron

AU - Litterman, Nadia K.

AU - McIntyre, Matthew H.

AU - Mountain, Joanna L.

AU - Northover, Carrie A.M.

AU - Sathirapongsasuti, J. Fah

AU - Sazonova, Olga V.

AU - Shelton, Janie F.

AU - Shringarpure, Suyash

AU - Tian, Chao

AU - Tung, Joyce Y.

AU - Vacic, Vladimir

AU - Wilson, Catherine H.

AU - Pitts, Steven J.

PY - 2018/2/1

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AB - 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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JO - Nature Genetics

JF - Nature Genetics

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ER -

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

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