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

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 DjurovicThomas 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, Christina M. Lill

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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.

Original languageEnglish
Article number2098
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 29 May 2018

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Keywords

  • cognitive neuroscience
  • genetics of the nervous system
  • Genome-wide association studies
  • quantitative trait

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