Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Gail Davies, Max Lam, Sarah E. Harris, Joey W. Trampush, Michelle Luciano, W. David Hill, Saskia P. Hagenaars, Stuart J. Ritchie, Riccardo E. Marioni, Chloe Fawns-Ritchie, David C. M. Liewald, Judith A. Okely, Ari V. Ahola-Olli, Catriona L. K. Barnes, Lars Bertram, Joshua C. Bis, Katherine E. Burdick, Andrea Christoforou, Pamela DeRosse, Srdjan Djurovic, Thomas Espeseth, Stella Giakoumaki, Sudheer Giddaluru, Daniel E. Gustavson, Caroline Hayward, Edith Hofer, M. Arfan Ikram, Robert Karlsson, Emma Knowles, Jari Lahti, Markus Leber, Shuo Li, Karen A. Mather, Ingrid Melle, Derek Morris, Christopher Oldmeadow, Teemu Palviainen, Antony Payton, Raha Pazoki, Katja Petrovic, Chandra A. Reynolds, Muralidharan Sargurupremraj, Markus Scholz, Jennifer A. Smith, Albert V. Smith, Natalie Terzikhan, Anbupalam Thalamuthu, Stella Trompet, Sven J. van der Lee, Erin B. Ware, B. Gwen Windham, Margaret J. Wright, Jingyun Yang, Jin Yu, David Ames, Najaf Amin, Philippe Amouyel, Ole A. Andreassen, Nicola J. Armstrong, Amelia A. Assareh, John R. Attia, Deborah Attix, Dimitrios Avramopoulos, David A. Bennett, Anne C. Böhmer, Patricia A. Boyle, Henry Brodaty, Harry Campbell, Tyrone D. Cannon, Elizabeth T. Cirulli, Eliza Congdon, Emily Drabant Conley, Janie Corley, Simon R. Cox, Anders M. Dale, Abbas Dehghan, Danielle Dick, Dwight Dickinson, Johan G. Eriksson, Evangelos Evangelou, Jessica D. Faul, Ian Ford, Nelson A. Freimer, He Gao, Ina Giegling, Nathan A. Gillespie, Scott D. Gordon, Rebecca F. Gottesman, Michael E. Griswold, Vilmundur Gudnason, Tamara B. Harris, Annette M. Hartmann, Alex Hatzimanolis, Gerardo Heiss, Elizabeth G. Holliday, Peter K. Joshi, Mika Kähönen, Sharon L. R. Kardia, Ida Karlsson, Luca Kleineidam, David S. Knopman, Nicole A. Kochan, Bettina Konte, John B. Kwok, Stephanie Le Hellard, Teresa Lee, Terho Lehtimäki, Shu-Chen Li, Tian Liu, Marisa Koini, Edythe London, Will T. Longstreth, Oscar L. Lopez, Anu Loukola, Tobias Luck, Astri J. Lundervold, Anders Lundquist, Leo-Pekka Lyytikäinen, Nicholas G. Martin, Grant W. Montgomery, Alison D. Murray, Anna C. Need, Raymond Noordam, Lars Nyberg, William Ollier, Goran Papenberg, Alison Pattie, Ozren Polasek, Russell A. Poldrack, Bruce M. Psaty, Simone Reppermund, Steffi G. Riedel-Heller, Richard J. Rose, Jerome I. Rotter, Panos Roussos, Suvi P. Rovio, Yasaman Saba, Fred W. Sabb, Perminder S. Sachdev, Claudia L. Satizabal, Matthias Schmid, Rodney J. Scott, Matthew A. Scult, Jeannette Simino, P. Eline Slagboom, Nikolaos Smyrnis, Aïcha Soumaré, Nikos C. Stefanis, David J. Stott, Richard E. Straub, Kjetil Sundet, Adele M. Taylor, Kent D. Taylor, Ioanna Tzoulaki, Christophe Tzourio, André Uitterlinden, Veronique Vitart, Aristotle N. Voineskos, Jaakko Kaprio, Michael Wagner, Holger Wagner, Leonie Weinhold, K. Hoyan Wen, Elisabeth Widen, Qiong Yang, Wei Zhao, Hieab H. H. Adams, Dan E. Arking, Robert M. Bilder, Panos Bitsios, Eric Boerwinkle, Ornit Chiba-Falek, Aiden Corvin, Philip L. De Jager, Stéphanie Debette, Gary Donohoe, Paul Elliott, Annette L. Fitzpatrick, Michael Gill, David C. Glahn, Sara Hägg, Narelle K. Hansell, Ahmad R. Hariri, M. Kamran Ikram, J. Wouter Jukema, Eero Vuoksimaa, Matthew C. Keller, William S. Kremen, Lenore Launer, Ulman Lindenberger, Aarno Palotie, Nancy L. Pedersen, Neil Pendleton, David J. Porteous, Katri Räikkönen, Olli T. Raitakari, Alfredo Ramirez, Ivar Reinvang, Igor Rudan, Dan Rujescu, Reinhold Schmidt, Helena Schmidt, Peter W. Schofield, Peter R. Schofield, John M. Starr, Vidar M. Steen, Julian N. Trollor, Steven T. Turner, Cornelia M. Van Duijn, Arno Villringer, Daniel R. Weinberger, David R. Weir, James F. Wilson, Anil Malhotra, Andrew M. McIntosh, Catharine R. Gale, Sudha Seshadri, Thomas H. Mosley, Jan Bressler, Todd Lencz, Ian J. Deary

ABSTRACT

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function. More... »

PAGES

2098

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    9

    Author Affiliations

  • University of Edinburgh
  • Institute of Mental Health
  • University of Southern California
  • King's College London
  • Satakunta Central Hospital
  • Max Planck Institute for Molecular Genetics
  • University of Washington
  • James J Peters VA Medical Center
  • Haukeland University Hospital
  • Feinstein Institute for Medical Research
  • Oslo University Hospital
  • University of Crete
  • Medical University of Graz
  • Erasmus University Medical Center
  • Karolinska Institute
  • Yale University
  • University of Helsinki
  • University of Cologne
  • Boston University
  • UNSW Australia
  • University of Bergen
  • National University of Ireland, Galway
  • University of Newcastle Australia
  • University of Manchester
  • Imperial College London
  • University of California, Riverside
  • University of Bordeaux
  • Leipzig University
  • University of Michigan–Ann Arbor
  • University of Iceland
  • Ghent University Hospital
  • Leiden University Medical Center
  • University of Mississippi Medical Center
  • University of Queensland
  • Rush University Medical Center
  • University of Melbourne
  • Centre Hospitalier Regional et Universitaire de Lille
  • Murdoch University
  • Duke University Hospital
  • Johns Hopkins University
  • University of Bonn
  • University of California Los Angeles
  • University of California, San Diego
  • Virginia Commonwealth University
  • Folkhälsans Forskningscentrum
  • National Institute for Health and Welfare
  • University of Glasgow
  • Martin Luther University Halle-Wittenberg
  • QIMR Berghofer Medical Research Institute
  • National Institutes of Health
  • University Mental Health Research Institute
  • University of North Carolina at Chapel Hill
  • University of Tampere
  • Mayo Clinic
  • Prince of Wales Hospital
  • TU Dresden
  • Max Planck Institute for Human Development
  • University of Pittsburgh
  • Umeå University
  • University of Aberdeen
  • Stockholm University
  • University of Split
  • Lucile Packard Children's Hospital
  • Kaiser Permanente Washington Health Research Institute
  • Indiana University Bloomington
  • Harbor–UCLA Medical Center
  • University of Turku
  • University of Oregon
  • National Heart Lung and Blood Institute
  • University Hospital Cologne
  • Duke University
  • Lieber Institute for Brain Development
  • University of Ioannina
  • Centre Hospitalier Universitaire de Bordeaux
  • University of Toronto
  • Baylor College of Medicine
  • Trinity College Dublin
  • Broad Institute
  • University of Colorado Boulder
  • Turku University Hospital
  • University Hospital Leipzig
  • Hofstra University
  • University of Southampton
  • The University of Texas Health Science Center at San Antonio
  • The University of Texas Health Science Center at Houston
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-04362-x

    DOI

    http://dx.doi.org/10.1038/s41467-018-04362-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1104192177

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29844566


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