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

Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
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.
Davies, Gail
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Lam, Max
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Harris, Sarah E.
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Trampush, Joey W
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Luciano, Michelle
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Hill, W David
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Hagenaars, Saskia P.
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Ritchie, Stuart J.
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Marioni, Riccardo E.
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Fawns-Ritchie, Chloe
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Liewald, David C M
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Okely, Judith A.
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Ahola-Olli, Ari V
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Barnes, Catriona L K
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Bertram, Lars
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Bis, Joshua C.
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Gale, Catharine
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Burdick, Katherine E
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Christoforou, Andrea
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DeRosse, Pamela
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Djurovic, Srdjan
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Espeseth, Thomas
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Giakoumaki, Stella
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Giddaluru, Sudheer
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Gustavson, Daniel E
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Hayward, Caroline
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Hofer, Edith
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Ikram, M Arfan
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Karlsson, Robert
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Knowles, Emma
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Lahti, Jari
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Leber, Markus
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Liu, Shuo
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Mather, Karen A.
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Melle, Ingrid
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Morris, Derek
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Oldmeadow, Christopher
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Palviainen, Teemu
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Payton, Antony
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Petrovic, Katja
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Reynolds, Chandra A
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Sargurupremraj, Muralidharan
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Scholz, Markus
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Smith, Jennifer A.
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Smith, Albert V
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Terzihan, Natalie
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Thalamuthu, Anbupalam
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Trompet, Stella
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van der Lee, Sven J
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et al.
Davies, Gail
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Lam, Max
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Harris, Sarah E.
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Trampush, Joey W
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Luciano, Michelle
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Hill, W David
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Hagenaars, Saskia P.
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Ritchie, Stuart J.
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Marioni, Riccardo E.
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Fawns-Ritchie, Chloe
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Liewald, David C M
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Okely, Judith A.
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Ahola-Olli, Ari V
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Barnes, Catriona L K
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Bertram, Lars
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Bis, Joshua C.
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Gale, Catharine
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Burdick, Katherine E
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Christoforou, Andrea
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DeRosse, Pamela
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Djurovic, Srdjan
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Espeseth, Thomas
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Giakoumaki, Stella
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Giddaluru, Sudheer
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Gustavson, Daniel E
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Hayward, Caroline
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Hofer, Edith
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Ikram, M Arfan
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Karlsson, Robert
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Knowles, Emma
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Lahti, Jari
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Leber, Markus
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Liu, Shuo
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Mather, Karen A.
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Melle, Ingrid
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Morris, Derek
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Oldmeadow, Christopher
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Palviainen, Teemu
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Payton, Antony
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Pazoki, Raha
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Petrovic, Katja
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Reynolds, Chandra A
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Sargurupremraj, Muralidharan
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Scholz, Markus
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Smith, Jennifer A.
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Smith, Albert V
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Terzihan, Natalie
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Thalamuthu, Anbupalam
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Trompet, Stella
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van der Lee, Sven J
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Davies, Gail, Lam, Max, Harris, Sarah E., Trampush, Joey W, Luciano, Michelle, Hill, W David, Hagenaars, Saskia P., Ritchie, Stuart J., Marioni, Riccardo E., Fawns-Ritchie, Chloe, Liewald, David C M, Okely, Judith A., Ahola-Olli, Ari V, Barnes, Catriona L K, Bertram, Lars, Bis, Joshua C., Gale, Catharine, Burdick, Katherine E, Christoforou, Andrea, DeRosse, Pamela, Djurovic, Srdjan, Espeseth, Thomas, Giakoumaki, Stella, Giddaluru, Sudheer, Gustavson, Daniel E, Hayward, Caroline, Hofer, Edith, Ikram, M Arfan, Karlsson, Robert, Knowles, Emma, Lahti, Jari, Leber, Markus, Liu, Shuo, Mather, Karen A., Melle, Ingrid, Morris, Derek, Oldmeadow, Christopher, Palviainen, Teemu, Payton, Antony, Pazoki, Raha, Petrovic, Katja, Reynolds, Chandra A, Sargurupremraj, Muralidharan, Scholz, Markus, Smith, Jennifer A., Smith, Albert V, Terzihan, Natalie, Thalamuthu, Anbupalam, Trompet, Stella and van der Lee, Sven J , et al. (2018) Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nature Communications. (doi:10.1038/s41467-018-04362-x).

Record type: Article

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.

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Accepted/In Press date: 23 April 2018
e-pub ahead of print date: 29 May 2018

Identifiers

Local EPrints ID: 426523
URI: https://eprints.soton.ac.uk/id/eprint/426523
PURE UUID: d4f34c7c-8c8e-417f-b8e7-590215cdddcf
ORCID for Catharine Gale: ORCID iD orcid.org/0000-0002-3361-8638

Catalogue record

Date deposited: 29 Nov 2018 17:30
Last modified: 10 Dec 2019 01:54

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Contributors

Author: Gail Davies
Author: Max Lam
Author: Sarah E. Harris
Author: Joey W Trampush
Author: Michelle Luciano
Author: W David Hill
Author: Saskia P. Hagenaars
Author: Stuart J. Ritchie
Author: Riccardo E. Marioni
Author: Chloe Fawns-Ritchie
Author: David C M Liewald
Author: Judith A. Okely
Author: Ari V Ahola-Olli
Author: Catriona L K Barnes
Author: Lars Bertram
Author: Joshua C. Bis
Author: Catharine Gale ORCID iD
Author: Katherine E Burdick
Author: Andrea Christoforou
Author: Pamela DeRosse
Author: Srdjan Djurovic
Author: Thomas Espeseth
Author: Stella Giakoumaki
Author: Sudheer Giddaluru
Author: Daniel E Gustavson
Author: Caroline Hayward
Author: Edith Hofer
Author: M Arfan Ikram
Author: Robert Karlsson
Author: Emma Knowles
Author: Jari Lahti
Author: Markus Leber
Author: Shuo Liu
Author: Karen A. Mather
Author: Ingrid Melle
Author: Derek Morris
Author: Christopher Oldmeadow
Author: Teemu Palviainen
Author: Antony Payton
Author: Raha Pazoki
Author: Katja Petrovic
Author: Chandra A Reynolds
Author: Muralidharan Sargurupremraj
Author: Markus Scholz
Author: Jennifer A. Smith
Author: Albert V Smith
Author: Natalie Terzihan
Author: Anbupalam Thalamuthu
Author: Stella Trompet
Author: Sven J van der Lee

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