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A global overview of pleiotropy and genetic architecture in complex traits

View ORCID ProfileKyoko Watanabe, Sven Stringer, View ORCID ProfileOleksandr Frei, Maša Umićević Mirkov, View ORCID ProfileTinca J.C. Polderman, View ORCID ProfileSophie van der Sluis, View ORCID ProfileOle A. Andreassen, View ORCID ProfileBenjamin M. Neale, View ORCID ProfileDanielle Posthuma
doi: https://doi.org/10.1101/500090
Kyoko Watanabe
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, The Netherlands
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Sven Stringer
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, The Netherlands
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Oleksandr Frei
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Criminal Medicine, University of Oslo, Oslo, Norway
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Maša Umićević Mirkov
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, The Netherlands
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Tinca J.C. Polderman
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, The Netherlands
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  • ORCID record for Tinca J.C. Polderman
Sophie van der Sluis
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, The NetherlandsDepartment of Clinical Genetics, Section of Complex Trait Genetics, Neuroscience Campus Amsterdam, VU Medical Center, Amsterdam, the Netherlands
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Ole A. Andreassen
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Criminal Medicine, University of Oslo, Oslo, NorwayDivision of Mental health and addiction Oslo University hospital, Oslo, Norway
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Benjamin M. Neale
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USAAnalytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USAStanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Danielle Posthuma
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, The NetherlandsDepartment of Clinical Genetics, Section of Complex Trait Genetics, Neuroscience Campus Amsterdam, VU Medical Center, Amsterdam, the Netherlands
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  • For correspondence: d.posthuma@vu.nl
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ABSTRACT

After a decade of genome-wide association studies (GWASs), fundamental questions in human genetics are still unanswered, such as the extent of pleiotropy across the genome, the nature of trait-associated genetic variants and the disparate genetic architecture across human traits. The current availability of hundreds of GWAS results provide the unique opportunity to gain insight into these questions. In this study, we harmonized and systematically analysed 4,155 publicly available GWASs. For a subset of well-powered GWAS on 558 unique traits, we provide an extensive overview of pleiotropy and genetic architecture. We show that trait associated loci cover more than half of the genome, and 90% of those loci are associated with multiple trait domains. We further show that potential causal genetic variants are enriched in coding and flanking regions, as well as in regulatory elements, and how trait-polygenicity is related to an estimate of the required sample size to detect 90% of causal genetic variants. Our results provide novel insights into how genetic variation contributes to trait variation. All GWAS results can be queried and visualized at the GWAS ATLAS resource (http://atlas.ctglab.nl).

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 19, 2018.
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A global overview of pleiotropy and genetic architecture in complex traits
Kyoko Watanabe, Sven Stringer, Oleksandr Frei, Maša Umićević Mirkov, Tinca J.C. Polderman, Sophie van der Sluis, Ole A. Andreassen, Benjamin M. Neale, Danielle Posthuma
bioRxiv 500090; doi: https://doi.org/10.1101/500090
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A global overview of pleiotropy and genetic architecture in complex traits
Kyoko Watanabe, Sven Stringer, Oleksandr Frei, Maša Umićević Mirkov, Tinca J.C. Polderman, Sophie van der Sluis, Ole A. Andreassen, Benjamin M. Neale, Danielle Posthuma
bioRxiv 500090; doi: https://doi.org/10.1101/500090

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