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; 23andMe Research Team; Social Science Genetic Association Consortium; Patrik Magnusson; Sven Oskarsson; Magnus Johannesson; Peter M Visscher; David Laibson; David Cesarini; Benjamin M Neale; Daniel J Benjamin

doi:10.1038/s41588-017-0009-4

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

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

Authors

Patrick Turley^{1

2}, Raymond K Walters^{3

4}, Omeed Maghzian⁵, Aysu Okbay⁶, James J Lee⁷, Mark Alan Fontana⁸, Tuan Anh Nguyen-Viet⁹, Robbee Wedow^{10

11

12}, Meghan Zacher¹³, Nicholas A Furlotte¹⁴; 23andMe Research Team; Social Science Genetic Association Consortium; Patrik Magnusson¹⁵, Sven Oskarsson¹⁶, Magnus Johannesson¹⁷, Peter M Visscher^{18

19}, David Laibson^{5

20}, David Cesarini^{21

22

23}, Benjamin M Neale^{24

25}, Daniel J Benjamin^{26

27

28}

Affiliations

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.

Publication types

Comparative Study
Evaluation Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Data Interpretation, Statistical*
Datasets as Topic / statistics & numerical data
Depression / epidemiology
Depression / genetics
Diagnostic Self Evaluation
Genetic Association Studies / methods
Genetic Association Studies / statistics & numerical data
Genome-Wide Association Study / methods*
Genome-Wide Association Study / statistics & numerical data*
Health / statistics & numerical data
Humans
Meta-Analysis as Topic
Multifactorial Inheritance*
Neuroticism
Phenotype
Polymorphism, Single Nucleotide
Quantitative Trait Loci* / genetics

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

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Abstract

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