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

• Published in: Nature genetics Vol. 50; no. 2; pp. 229 - 237
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2018; Nature Publishing Group
• Subjects: 631/208/205/2138; 631/208/212; 631/378; Accuracy; Agriculture; Algorithms; Animal Genetics and Genomics; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Comparative analysis; Computational biology; Data Interpretation, Statistical; Datasets as Topic - statistics & numerical data; Depression - epidemiology; Depression - genetics; Diagnostic Self Evaluation; Economic models; Gene Function; Genetic aspects; Genetic Association Studies - methods; Genetic Association Studies - statistics & numerical data; Genome-wide association studies; Genome-Wide Association Study - methods; Genome-Wide Association Study - statistics & numerical data; Genomes; Genomics; Health - statistics & numerical data; Human Genetics; Humans; Loci; Mental depression; Meta-analysis; Meta-Analysis as Topic; Multifactorial Inheritance; Neurosis; Neuroticism; Phenotype; Polygenic inheritance; Polymorphism, Single Nucleotide; Psychological factors; Quantitative Trait Loci - genetics; Statistical analysis; Statistical methods; Statistics; Well being; Sweden
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/s41588-017-0009-4

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. MTAG is a new method for joint analysis of summary statistics from genome-wide association studies of different traits. Applying MTAG to summary statistics for depressive symptoms, neuroticism and subjective well-being increased discovery of associated loci as compared to single-trait analyses.