New Results
GWAS meta-analysis (N=279,930) identifies new genes and functional links to intelligence
Jeanne E. Savage, Philip R. Jansen, Sven Stringer, Kyoko Watanabe, Julien Bryois, Christiaan A. de Leeuw, Mats Nagel, Swapnil Awasthi, Peter B. Barr, Jonathan R. I. Coleman, Katrina L. Grasby, Anke R. Hammerschlag, Jakob Kaminski, Robert Karlsson, Eva Krapohl, Max Lam, Marianne Nygaard, Chandra A. Reynolds, Joey W. Trampush, Hannah Young, Delilah Zabaneh, Sara Hägg, Narelle K. Hansell, Ida K. Karlsson, Sten Linnarsson, Grant W. Montgomery, Ana B. Munoz-Manchado, Erin B. Quinlan, Gunter Schumann, Nathan Skene, Bradley T. Webb, Tonya White, Dan E. Arking, Deborah K. Attix, Dimitrios Avramopoulos, Robert M. Bilder, Panos Bitsios, Katherine E. Burdick, Tyrone D. Cannon, Ornit Chiba-Falek, Andrea Christoforou, Elizabeth T. Cirulli, Eliza Congdon, Aiden Corvin, Gail Davies, Ian J. Deary, Pamela DeRosse, Dwight Dickinson, Srdjan Djurovic, Gary Donohoe, Emily Drabant Conley, Johan G. Eriksson, Thomas Espeseth, Nelson A. Freimer, Stella Giakoumaki, Ina Giegling, Michael Gill, David C. Glahn, Ahmad R. Hariri, Alex Hatzimanolis, Matthew C. Keller, Emma Knowles, Bettina Konte, Jari Lahti, Stephanie Le Hellard, Todd Lencz, David C. Liewald, Edythe London, Astri J. Lundervold, Anil K. Malhotra, Ingrid Melle, Derek Morris, Anna C. Need, William Ollier, Aarno Palotie, Antony Payton, Neil Pendleton, Russell A. Poldrack, Katri Räikkönen, Ivar Reinvang, Panos Roussos, Dan Rujescu, Fred W. Sabb, Matthew A. Scult, Olav B. Smeland, Nikolaos Smyrnis, John M. Starr, Vidar M. Steen, Nikos C. Stefanis, Richard E. Straub, Kjetil Sundet, Aristotle N. Voineskos, Daniel R. Weinberger, Elisabeth Widen, Jin Yu, Goncalo Abecasis, Ole A. Andreassen, Gerome Breen, Lene Christiansen, Birgit Debrabant, Danielle M. Dick, Andreas Heinz, Jens Hjerling-Leffler, M. Arfan Ikram, Kenneth S. Kendler, Nicholas G. Martin, Sarah E. Medland, Nancy L. Pedersen, Robert Plomin, Tinca J. C. Polderman, Stephan Ripke, Sophie van der Sluis, Patrick F. Sullivan, Henning Tiemeier, Scott I. Vrieze, Margaret J. Wright, Danielle Posthuma
doi: https://doi.org/10.1101/184853
Jeanne E. Savage
VU University;
Philip R. Jansen
VU University;
Sven Stringer
VU University;
Kyoko Watanabe
VU University;
Julien Bryois
Karolinska Institutet;
Christiaan A. de Leeuw
VU University;
Mats Nagel
VU University;
Swapnil Awasthi
Charite Universitatsmedizin Berlin;
Peter B. Barr
Virginia Commonwealth University;
Jonathan R. I. Coleman
King's College London;
Katrina L. Grasby
QIMR Berghofer Medical Research Institute;
Anke R. Hammerschlag
VU University;
Jakob Kaminski
Charite Universitatsmedizin Berlin;
Robert Karlsson
Karolinska Institutet;
Eva Krapohl
King's College London;
Max Lam
Institute of Mental Health;
Marianne Nygaard
University of Southern Denmark;
Chandra A. Reynolds
University of California Riverside;
Joey W. Trampush
BrainWorkup;
Hannah Young
University of Colorado, Boulder;
Delilah Zabaneh
King's College London;
Sara Hägg
Karolinska Institutet;
Narelle K. Hansell
QIMR;
Ida K. Karlsson
Karolinska Institutet;
Sten Linnarsson
Karolinska Institutet;
Grant W. Montgomery
QIMR;
Ana B. Munoz-Manchado
Karolinska Institutet;
Erin B. Quinlan
King's College London;
Gunter Schumann
King's College London;
Nathan Skene
Karolinska Institutet;
Bradley T. Webb
Virginia Commonwealth University;
Tonya White
Erasmus Medical Center;
Dan E. Arking
Johns Hopkins University School of Medicine;
Deborah K. Attix
Haukeland University Hospital;
Dimitrios Avramopoulos
Johns Hopkins University School of Medicine;
Robert M. Bilder
UCLA Semel Institute for Neuroscience and Human Behavior;
Panos Bitsios
University of Crete;
Katherine E. Burdick
Icahn School of Medicine at Mount Sinai;
Tyrone D. Cannon
Yale University;
Ornit Chiba-Falek
Duke University Medical Center;
Andrea Christoforou
Haukeland University Hospital;
Elizabeth T. Cirulli
Human Longevity, Inc.;
Eliza Congdon
UCLA Semel Institute for Neuroscience and Human Behavior;
Aiden Corvin
Trinity College Dublin;
Gail Davies
University of Edinburgh;
Ian J. Deary
University of Edinburgh;
Pamela DeRosse
The Zucker Hillside Hospital;
Dwight Dickinson
National Institute of Mental Health;
Srdjan Djurovic
University of Bergen;
Gary Donohoe
National University of Ireland;
Emily Drabant Conley
23andMe;
Johan G. Eriksson
University of Helsinki;
Thomas Espeseth
Oslo University Hospital;
Nelson A. Freimer
UCLA Semel Institute for Neuroscience and Human Behavior;
Stella Giakoumaki
University of Crete;
Ina Giegling
Martin Luther University of Halle-Wittenberg;
Michael Gill
Trinity College Dublin;
David C. Glahn
Yale University School of Medicine;
Ahmad R. Hariri
Duke University;
Alex Hatzimanolis
Eginition Hospital;
Matthew C. Keller
University of Colorado;
Emma Knowles
Yale University School of Medicine;
Bettina Konte
Martin Luther University of Halle-Wittenberg;
Jari Lahti
University of Helsinki;
Stephanie Le Hellard
University of Bergen;
Todd Lencz
The Zucker Hillside Hospital;
David C. Liewald
University of Edinburgh;
Edythe London
UCLA Semel Institute for Neuroscience and Human Behavior;
Astri J. Lundervold
University of Bergen;
Anil K. Malhotra
The Zucker Hillside Hospital;
Ingrid Melle
University of Bergen;
Derek Morris
National University of Ireland;
Anna C. Need
Imperial College;
William Ollier
University of Manchester;
Aarno Palotie
University of Helsinki;
Antony Payton
University of Manchester;
Neil Pendleton
University of Manchester;
Russell A. Poldrack
Stanford University;
Katri Räikkönen
University of Helsinki;
Ivar Reinvang
University of Oslo;
Panos Roussos
Icahn School of Medicine at Mount Sinai;
Dan Rujescu
Martin Luther University of Halle-Wittenberg;
Fred W. Sabb
University of Oregon;
Matthew A. Scult
Duke University;
Olav B. Smeland
Oslo University Hospital;
Nikolaos Smyrnis
Eginition Hospital;
John M. Starr
University of Edinburgh;
Vidar M. Steen
University of Bergen;
Nikos C. Stefanis
Eginition Hospital;
Richard E. Straub
Johns Hopkins University Medical Campus;
Kjetil Sundet
Oslo University Hospital;
Aristotle N. Voineskos
University of Toronto;
Daniel R. Weinberger
Johns Hopkins University Medical Campus;
Elisabeth Widen
University of Helsinki;
Jin Yu
The Zucker Hillside Hospital;
Goncalo Abecasis
University of Michigan;
Ole A. Andreassen
K. G. Jebsen Centre for Psychosis Research;
Gerome Breen
King's College London;
Lene Christiansen
University of Southern Denmark;
Birgit Debrabant
University of Southern Denmark;
Danielle M. Dick
Virginia Commonwealth University;
Andreas Heinz
Charite Universitatsmedizin Berlin;
Jens Hjerling-Leffler
Karolinska Institutet;
M. Arfan Ikram
Erasmus University Medical Center;
Kenneth S. Kendler
Virginia Commonwealth University;
Nicholas G. Martin
QIMR Berghofer Medical Research Institute;
Sarah E. Medland
QIMR Berghofer Medical Research Institute;
Nancy L. Pedersen
Karolinska Institutet;
Robert Plomin
King's College London;
Tinca J. C. Polderman
VU University;
Stephan Ripke
Charite Universitatsmedizin Berlin;
Sophie van der Sluis
VU University;
Patrick F. Sullivan
Karolinska Institutet;
Henning Tiemeier
Erasmus Medical Center;
Scott I. Vrieze
University of Colorado Boulder
Margaret J. Wright
QIMR;
Danielle Posthuma
VU University;
Abstract
Intelligence is highly heritable and a major determinant of human health and well-being. Recent genome-wide meta-analyses have identified 24 genomic loci linked to intelligence, but much about its genetic underpinnings remains to be discovered. Here, we present the largest genetic association study of intelligence to date (N=279,930), identifying 206 genomic loci (191 novel) and implicating 1,041 genes (963 novel) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and identify 89 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain and specifically in striatal medium spiny neurons and cortical and hippocampal pyramidal neurons. Gene-set analyses implicate pathways related to neurogenesis, neuron differentiation and synaptic structure. We confirm previous strong genetic correlations with several neuropsychiatric disorders, and Mendelian Randomization results suggest protective effects of intelligence for Alzheimer's dementia and ADHD, and bidirectional causation with strong pleiotropy for schizophrenia. These results are a major step forward in understanding the neurobiology of intelligence as well as genetically associated neuropsychiatric traits.
Copyright
The copyright holder for this preprint is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.
- Posted September 6, 2017.
GWAS meta-analysis (N=279,930) identifies new genes and functional links to intelligence
Jeanne E. Savage, Philip R. Jansen, Sven Stringer, Kyoko Watanabe, Julien Bryois, Christiaan A. de Leeuw, Mats Nagel, Swapnil Awasthi, Peter B. Barr, Jonathan R. I. Coleman, Katrina L. Grasby, Anke R. Hammerschlag, Jakob Kaminski, Robert Karlsson, Eva Krapohl, Max Lam, Marianne Nygaard, Chandra A. Reynolds, Joey W. Trampush, Hannah Young, Delilah Zabaneh, Sara Hägg, Narelle K. Hansell, Ida K. Karlsson, Sten Linnarsson, Grant W. Montgomery, Ana B. Munoz-Manchado, Erin B. Quinlan, Gunter Schumann, Nathan Skene, Bradley T. Webb, Tonya White, Dan E. Arking, Deborah K. Attix, Dimitrios Avramopoulos, Robert M. Bilder, Panos Bitsios, Katherine E. Burdick, Tyrone D. Cannon, Ornit Chiba-Falek, Andrea Christoforou, Elizabeth T. Cirulli, Eliza Congdon, Aiden Corvin, Gail Davies, Ian J. Deary, Pamela DeRosse, Dwight Dickinson, Srdjan Djurovic, Gary Donohoe, Emily Drabant Conley, Johan G. Eriksson, Thomas Espeseth, Nelson A. Freimer, Stella Giakoumaki, Ina Giegling, Michael Gill, David C. Glahn, Ahmad R. Hariri, Alex Hatzimanolis, Matthew C. Keller, Emma Knowles, Bettina Konte, Jari Lahti, Stephanie Le Hellard, Todd Lencz, David C. Liewald, Edythe London, Astri J. Lundervold, Anil K. Malhotra, Ingrid Melle, Derek Morris, Anna C. Need, William Ollier, Aarno Palotie, Antony Payton, Neil Pendleton, Russell A. Poldrack, Katri Räikkönen, Ivar Reinvang, Panos Roussos, Dan Rujescu, Fred W. Sabb, Matthew A. Scult, Olav B. Smeland, Nikolaos Smyrnis, John M. Starr, Vidar M. Steen, Nikos C. Stefanis, Richard E. Straub, Kjetil Sundet, Aristotle N. Voineskos, Daniel R. Weinberger, Elisabeth Widen, Jin Yu, Goncalo Abecasis, Ole A. Andreassen, Gerome Breen, Lene Christiansen, Birgit Debrabant, Danielle M. Dick, Andreas Heinz, Jens Hjerling-Leffler, M. Arfan Ikram, Kenneth S. Kendler, Nicholas G. Martin, Sarah E. Medland, Nancy L. Pedersen, Robert Plomin, Tinca J. C. Polderman, Stephan Ripke, Sophie van der Sluis, Patrick F. Sullivan, Henning Tiemeier, Scott I. Vrieze, Margaret J. Wright, Danielle Posthuma
bioRxiv 184853; doi: https://doi.org/10.1101/184853
Permalink:
GWAS meta-analysis (N=279,930) identifies new genes and functional links to intelligence
Jeanne E. Savage, Philip R. Jansen, Sven Stringer, Kyoko Watanabe, Julien Bryois, Christiaan A. de Leeuw, Mats Nagel, Swapnil Awasthi, Peter B. Barr, Jonathan R. I. Coleman, Katrina L. Grasby, Anke R. Hammerschlag, Jakob Kaminski, Robert Karlsson, Eva Krapohl, Max Lam, Marianne Nygaard, Chandra A. Reynolds, Joey W. Trampush, Hannah Young, Delilah Zabaneh, Sara Hägg, Narelle K. Hansell, Ida K. Karlsson, Sten Linnarsson, Grant W. Montgomery, Ana B. Munoz-Manchado, Erin B. Quinlan, Gunter Schumann, Nathan Skene, Bradley T. Webb, Tonya White, Dan E. Arking, Deborah K. Attix, Dimitrios Avramopoulos, Robert M. Bilder, Panos Bitsios, Katherine E. Burdick, Tyrone D. Cannon, Ornit Chiba-Falek, Andrea Christoforou, Elizabeth T. Cirulli, Eliza Congdon, Aiden Corvin, Gail Davies, Ian J. Deary, Pamela DeRosse, Dwight Dickinson, Srdjan Djurovic, Gary Donohoe, Emily Drabant Conley, Johan G. Eriksson, Thomas Espeseth, Nelson A. Freimer, Stella Giakoumaki, Ina Giegling, Michael Gill, David C. Glahn, Ahmad R. Hariri, Alex Hatzimanolis, Matthew C. Keller, Emma Knowles, Bettina Konte, Jari Lahti, Stephanie Le Hellard, Todd Lencz, David C. Liewald, Edythe London, Astri J. Lundervold, Anil K. Malhotra, Ingrid Melle, Derek Morris, Anna C. Need, William Ollier, Aarno Palotie, Antony Payton, Neil Pendleton, Russell A. Poldrack, Katri Räikkönen, Ivar Reinvang, Panos Roussos, Dan Rujescu, Fred W. Sabb, Matthew A. Scult, Olav B. Smeland, Nikolaos Smyrnis, John M. Starr, Vidar M. Steen, Nikos C. Stefanis, Richard E. Straub, Kjetil Sundet, Aristotle N. Voineskos, Daniel R. Weinberger, Elisabeth Widen, Jin Yu, Goncalo Abecasis, Ole A. Andreassen, Gerome Breen, Lene Christiansen, Birgit Debrabant, Danielle M. Dick, Andreas Heinz, Jens Hjerling-Leffler, M. Arfan Ikram, Kenneth S. Kendler, Nicholas G. Martin, Sarah E. Medland, Nancy L. Pedersen, Robert Plomin, Tinca J. C. Polderman, Stephan Ripke, Sophie van der Sluis, Patrick F. Sullivan, Henning Tiemeier, Scott I. Vrieze, Margaret J. Wright, Danielle Posthuma
bioRxiv 184853; doi: https://doi.org/10.1101/184853
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