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 (Neff = 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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We thank J. Beauchamp, P. Koellinger, Ö. Sandewall, C. Shulman, and R. de Vlaming for helpful comments and P. Bowers, E. Kong, T. Kundu, S. Lee, H. Li, R. Li, and R. Royer for research assistance. This research was carried out under the auspices of the Social Science Genetic Association Consortium (SSGAC). The study was supported by the Ragnar Söderberg Foundation (E9/11, M.J.; E42/15, D.C.), the Swedish Research Council (421-2013-1061, M.J.), the Jan Wallander and Tom Hedelius Foundation (M.J.), an ERC Consolidator Grant (647648 EdGe, P. Koellinger), the Pershing Square Fund of the Foundations of Human Behavior (D.L.), the National Science Foundation’s Graduate Research Fellowship Program (DGE 1144083, R.W.), and the NIA/NIH through grants P01-AG005842, P01-AG005842-20S2, and T32-AG000186-23 to D. Wise at NBER; P30-AG012810 (D.L.) to NBER; R01-AG042568-02 (D.J.B.) to the University of Southern California; and 1R01-MH107649-03 (B.M.N.), 1R01-MH101244-02 (B.M.N.), and 5U01-MH109539-02 (B.M.N.) to the Broad Institute at Harvard and MIT. This research has also been conducted using the UK Biobank Resource under application number 11425. We thank the research participants and employees of 23andMe for making this work possible. We also thank K. Mullan Harris and Add Health for early access to the data used in our replication and prediction analyses. A full list of acknowledgements is provided in the Supplementary Note.
B.M.N. is on the Scientific Advisory Board of Deep Genomics.
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23andMe Research Team:
Michelle Agee12, Babak Alipanahi12, Adam Auton12, Robert K. Bell12, Katarzyna Bryc12, Sarah L. Elson12, Pierre Fontanillas12, Nicholas A. Furlotte12, David A. Hinds12, Bethann S. Hromatka12, Karen E. Huber12, Aaron Kleinman12, Nadia K. Litterman12, Matthew H. McIntyre12, Joanna L. Mountain12, Carrie A. M. Northover12, J. Fah Sathirapongsasuti12, Olga V. Sazonova12, Janie F. Shelton12, Suyash Shringarpure12, Chao Tian12, Joyce Y. Tung12, Vladimir Vacic12, Catherine H. Wilson12 and Steven J. Pitts12
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Turley, P., Walters, R.K., Maghzian, O. et al. Multi-trait analysis of genome-wide association summary statistics using MTAG. Nat Genet 50, 229–237 (2018). https://doi.org/10.1038/s41588-017-0009-4
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