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GWAS of brain volume on 54,407 individuals and cross-trait analysis with intelligence identifies shared genomic loci and genes

Philip R Jansen, Mats Nagel, Kyoko Watanabe, Yongbin Wei, Jeanne E Savage, Christiaan A de Leeuw, Martijn P van den Heuvel, Sophie van der Sluis, Danielle Posthuma
doi: https://doi.org/10.1101/613489
Philip R Jansen
1Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands
2Department of Clinical Genetics, Section Complex Trait Genetics, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam UMC, Amsterdam, the Netherlands
3Department of Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, the Netherlands
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Mats Nagel
1Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands
2Department of Clinical Genetics, Section Complex Trait Genetics, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam UMC, Amsterdam, the Netherlands
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Kyoko Watanabe
1Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands
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Yongbin Wei
4Connectome Group, Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, the Netherlands
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Jeanne E Savage
1Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands
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Christiaan A de Leeuw
1Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands
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Martijn P van den Heuvel
2Department of Clinical Genetics, Section Complex Trait Genetics, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam UMC, Amsterdam, the Netherlands
4Connectome Group, Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, the Netherlands
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Sophie van der Sluis
1Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands
2Department of Clinical Genetics, Section Complex Trait Genetics, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam UMC, Amsterdam, the Netherlands
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Danielle Posthuma
1Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit, Amsterdam, The Netherlands
2Department of Clinical Genetics, Section Complex Trait Genetics, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam UMC, Amsterdam, the Netherlands
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  • For correspondence: d.posthuma@vu.nl
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Abstract

The phenotypic correlation between human intelligence and brain volume (BV) is considerable (r≈0.40), and has been shown to be due to shared genetic factors1. To further examine specific genetic factors driving this correlation, we present genomic analyses of the genetic overlap between intelligence and BV using genome-wide association study (GWAS) results. First, we conducted the largest BV GWAS meta-analysis to date (N=54,407 individuals), followed by functional annotation and gene-mapping. We identified 35 genomic loci (27 novel), implicating 362 genes (346 novel) and 23 biological pathways for BV. Second, we used an existing GWAS for intelligence (N=269,867 individuals2), and estimated the genetic correlation (rg) between BV and intelligence to be 0.23. We show that the rg is driven by physical overlap of GWAS hits in 5 genomic loci. We identified 67 shared genes between BV and intelligence, which are mainly involved in important signaling pathways regulating cell growth. Out of these 67 we prioritized 32 that are most likely to have functional impact. These results provide new information on the genetics of BV and provide biological insight into BV’s shared genetic etiology with intelligence.

Footnotes

  • ↵§ These authors jointly supervised this work

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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 April 19, 2019.
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GWAS of brain volume on 54,407 individuals and cross-trait analysis with intelligence identifies shared genomic loci and genes
Philip R Jansen, Mats Nagel, Kyoko Watanabe, Yongbin Wei, Jeanne E Savage, Christiaan A de Leeuw, Martijn P van den Heuvel, Sophie van der Sluis, Danielle Posthuma
bioRxiv 613489; doi: https://doi.org/10.1101/613489
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GWAS of brain volume on 54,407 individuals and cross-trait analysis with intelligence identifies shared genomic loci and genes
Philip R Jansen, Mats Nagel, Kyoko Watanabe, Yongbin Wei, Jeanne E Savage, Christiaan A de Leeuw, Martijn P van den Heuvel, Sophie van der Sluis, Danielle Posthuma
bioRxiv 613489; doi: https://doi.org/10.1101/613489

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