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Nat Genet. 2018 Feb;50(2):229-237. doi: 10.1038/s41588-017-0009-4. Epub 2018 Jan 1.

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

Author information

1
Broad Institute, Cambridge, MA, USA. paturley@broadinstitute.org.
2
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Cambridge, MA, USA. paturley@broadinstitute.org.
3
Broad Institute, Cambridge, MA, USA.
4
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Cambridge, MA, USA.
5
Department of Economics, Harvard University, Cambridge, MA, USA.
6
Department of Complex Trait Genetics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
7
Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
8
Hospital for Special Surgery, New York, NY, USA.
9
Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA.
10
Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
11
Institute of Behavioral Science, University of Colorado Boulder, Boulder, CO, USA.
12
Department of Sociology, University of Colorado Boulder, Boulder, CO, USA.
13
Department of Sociology, Harvard University, Cambridge, MA, USA.
14
23andMe, Inc., Mountain View, CA, USA.
15
Institutionen för Medicinsk Epidemiologi och Biostatistik, Karolinska Institutet, Stockholm, Sweden.
16
Department of Government, Uppsala Universitet, Uppsala, Sweden.
17
Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
18
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
19
Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
20
National Bureau of Economic Research, Cambridge, MA, USA.
21
National Bureau of Economic Research, Cambridge, MA, USA. dac12@nyu.edu.
22
Department of Economics and Center for Experimental Social Science, New York University, New York, NY, USA. dac12@nyu.edu.
23
Institutet för Näringslivsforskning, Stockholm, Sweden. dac12@nyu.edu.
24
Broad Institute, Cambridge, MA, USA. bneale@broadinstitute.org.
25
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Cambridge, MA, USA. bneale@broadinstitute.org.
26
Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA. daniel.benjamin@gmail.com.
27
National Bureau of Economic Research, Cambridge, MA, USA. daniel.benjamin@gmail.com.
28
Department of Economics, University of Southern California, Los Angeles, CA, USA. daniel.benjamin@gmail.com.

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.

PMID:
29292387
PMCID:
PMC5805593
DOI:
10.1038/s41588-017-0009-4
[Indexed for MEDLINE]
Free PMC Article

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