Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
24399044
TITLE
Human cognitive ability is influenced by genetic variation in components of postsynaptic signalling complexes assembled by NMDA receptors and MAGUK proteins.
ABSTRACT
Differences in general cognitive ability (intelligence) account for approximately half of the variation in any large battery of cognitive tests and are predictive of important life events including health. Genome-wide analyses of common single-nucleotide polymorphisms indicate that they jointly tag between a quarter and a half of the variance in intelligence. However, no single polymorphism has been reliably associated with variation in intelligence. It remains possible that these many small effects might be aggregated in networks of functionally linked genes. Here, we tested a network of 1461 genes in the postsynaptic density and associated complexes for an enriched association with intelligence. These were ascertained in 3511 individuals (the Cognitive Ageing Genetics in England and Scotland (CAGES) consortium) phenotyped for general cognitive ability, fluid cognitive ability, crystallised cognitive ability, memory and speed of processing. By analysing the results of a genome wide association study (GWAS) using Gene Set Enrichment Analysis, a significant enrichment was found for fluid cognitive ability for the proteins found in the complexes of N-methyl-D-aspartate receptor complex; P=0.002. Replication was sought in two additional cohorts (N=670 and 2062). A meta-analytic P-value of 0.003 was found when these were combined with the CAGES consortium. The results suggest that genetic variation in the macromolecular machines formed by membrane-associated guanylate kinase (MAGUK) scaffold proteins and their interaction partners contributes to variation in intelligence.
DATE PUBLISHED
2014
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2013/05/01
revised 2013/09/12
accepted 2013/10/21
entrez 2014/01/09 06:00
pubmed 2014/01/09 06:00
medline 2014/01/09 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Hill WD Hill W D WD Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Davies G Davies G G 1] Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK [2] Medical Genetics Section, The University of Edinburgh Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital Edinburgh, Edinburgh, UK.
van de Lagemaat LN van de Lagemaat L N LN Genes to Cognition Programme, Centre for Clinical Brain Sciences and Centre for Neuroregeneration The University of Edinburgh, Edinburgh, UK.
Christoforou A Christoforou A A 1] Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway [2] Dr E. Martens Research Group for Biological Psychiatry, Department of Clinical Science, University of Bergen, Bergen, Norway.
Marioni RE Marioni R E RE 1] Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK [2] Medical Genetics Section, The University of Edinburgh Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital Edinburgh, Edinburgh, UK [3] Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
Fernandes CP Fernandes C P D CP 1] Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway [2] Dr E. Martens Research Group for Biological Psychiatry, Department of Clinical Science, University of Bergen, Bergen, Norway.
Liewald DC Liewald D C DC Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Croning MD Croning M D R MD Genes to Cognition Programme, Centre for Clinical Brain Sciences and Centre for Neuroregeneration The University of Edinburgh, Edinburgh, UK.
Payton A Payton A A Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
Craig LC Craig L C A LC Public Health Nutrition Research Group Section of Population Health, University of Aberdeen, Aberdeen, UK.
Whalley LJ Whalley L J LJ Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK.
Horan M Horan M M Centre for Clinical and Cognitive Neurosciences, Institute Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
Ollier W Ollier W W Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
Hansell NK Hansell N K NK Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Wright MJ Wright M J MJ Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Martin NG Martin N G NG Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Montgomery GW Montgomery G W GW Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Steen VM Steen V M VM 1] Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway [2] Dr E. Martens Research Group for Biological Psychiatry, Department of Clinical Science, University of Bergen, Bergen, Norway.
Le Hellard S Le Hellard S S 1] Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway [2] Dr E. Martens Research Group for Biological Psychiatry, Department of Clinical Science, University of Bergen, Bergen, Norway.
Espeseth T Espeseth T T 1] Department of Psychology, University of Oslo, Oslo, Norway [2] KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.
Lundervold AJ Lundervold A J AJ 1] Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway [2] Kavli Research Centre for Aging and Dementia, Haraldplass Hospital, Bergen, Norway.
Reinvang I Reinvang I I Department of Psychology, University of Oslo, Oslo, Norway.
Starr JM Starr J M JM Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Pendleton N Pendleton N N Centre for Clinical and Cognitive Neurosciences, Institute Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
Grant SG Grant S G N SG Genes to Cognition Programme, Centre for Clinical Brain Sciences and Centre for Neuroregeneration The University of Edinburgh, Edinburgh, UK.
Bates TC Bates T C TC Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Deary IJ Deary I J IJ Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
INVESTIGATORS
JOURNAL
VOLUME: 4
ISSUE:
TITLE: Translational psychiatry
ISOABBREVIATION: Transl Psychiatry
YEAR: 2014
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2158-3188
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Transl Psychiatry
COUNTRY: United States
ISSNLINKING: 2158-3188
NLMUNIQUEID: 101562664
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Nat Genet. 2002 Jan;30(1):97-101 11731797
Cites Neuropharmacology. 2003 Jan;44(1):17-25 12559118
Cites J Pers Soc Psychol. 2004 Jan;86(1):130-47 14717632
Cites Am J Hum Genet. 2004 Aug;75(2):318-24 15185169
Cites J Neurochem. 2004 Oct;91(2):438-50 15447677
Cites Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11158-62 7972026
Cites Learn Mem. 1998 Sep-Oct;5(4-5):331-43 10454358
Cites Proteomics. 2005 Jul;5(10):2531-41 15984043
Cites Psychol Bull. 2005 Jul;131(4):592-617 16060804
Cites J Evol Biol. 2005 Sep;18(5):1368-73 16135132
Cites Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 16199517
Cites J Neurochem. 2006 Apr;97 Suppl 1:16-23 16635246
Cites Mol Syst Biol. 2006;2:2006.0023 16738568
Cites Twin Res Hum Genet. 2006 Jun;9(3):313-24 16790142
Cites Neuron. 2006 Nov 9;52(3):445-59 17088211
Cites Bioinformatics. 2007 May 15;23(10):1294-6 17384015
Cites Am J Hum Genet. 2007 Sep;81(3):559-75 17701901
Cites Annu Rev Cell Dev Biol. 2007;23:613-43 17506699
Cites J Neurosci Res. 2008 Jan;86(1):1-10 17663464
Cites BMC Geriatr. 2007;7:28 18053258
Cites Science. 2008 Apr 25;320(5875):539-43 18369103
Cites Nat Neurosci. 2008 Jul;11(7):799-806 18536710
Cites Neuron. 2008 Jul 10;59(1):84-97 18614031
Cites Genomics. 2008 Nov;92(5):265-72 18722519
Cites Mol Syst Biol. 2009;5:269 19455133
Cites Nature. 2009 Sep 10;461(7261):218-23 19741703
Cites Am J Hum Genet. 2007 Dec;81(6):1278-83 17966091
Cites PLoS One. 2011;6(4):e19011 21559497
Cites Maturitas. 2011 Aug;69(4):365-72 21700406
Cites J Evol Biol. 2011 Aug;24(8):1836-41 21605215
Cites Mol Psychiatry. 2011 Oct;16(10):996-1005 21826061
Cites Schizophr Res. 2011 Nov;132(2-3):220-7 21764562
Cites Annu Rev Psychol. 2012;63:453-82 21943169
Cites Mol Psychiatry. 2012 Feb;17(2):202-14 21647150
Cites Mol Psychiatry. 2012 Feb;17(2):142-53 22083728
Cites Neurosci Biobehav Rev. 2012 Mar;36(3):989-1000 22230702
Cites PLoS One. 2012;7(2):e31687 22384057
Cites Nat Genet. 2012 May;44(5):552-61 22504417
Cites Neurobiol Aging. 2012 Aug;33(8):1847.e1-14 22425255
Cites Annu Rev Neurosci. 2012;35:111-31 22715880
Cites Curr Opin Neurobiol. 2012 Jun;22(3):461-9 22217700
Cites Twin Res Hum Genet. 2012 Jun;15(3):442-52 22856377
Cites Mol Psychiatry. 2012 Oct;17(10):1026-30 22614288
Cites Psychol Sci. 2012;23(11):1314-23 23012269
Cites Nat Neurosci. 2013 Jan;16(1):25-32 23201971
Cites Nat Neurosci. 2013 Jan;16(1):16-24 23201973
Cites Int J Epidemiol. 2012 Dec;41(6):1576-84 22253310
Cites Neuropharmacology. 2013 Mar;66:65-81 22743159
Cites Biol Psychiatry. 2013 May 15;73(10):938-43 23419543
Cites Psychol Med. 2013 Dec;43(12):2563-70 23410598
Cites Mol Psychiatry. 2014 Feb;19(2):253-8 23358156
Cites Am J Hum Genet. 2009 Nov;85(5):750-5 19896111
Cites Neurogenetics. 2010 May;11(2):251-5 19795139
Cites Am J Hum Genet. 2010 Jul 9;87(1):139-45 20598278
Cites Bioinformatics. 2010 Sep 1;26(17):2190-1 20616382
Cites Arch Gen Psychiatry. 2010 Sep;67(9):905-13 20819984
Cites PLoS One. 2010;5(11):e13929 21085666
Cites Genet Epidemiol. 2010 Dec;34(8):816-34 21058334
Cites Nat Neurosci. 2011 Jan;14(1):19-21 21170055
Cites J Neurosci. 2000 Jun 1;20(11):3993-4001 10818134
Cites Nat Neurosci. 2000 Jul;3(7):661-9 10862698
Cites Br J Pharmacol. 2001 Feb;132(4):799-806 11181420
Cites Twin Res. 2001 Feb;4(1):48-56 11665325
Cites Biochem J. 2001 Nov 1;359(Pt 3):465-84 11672421
GRANTS
GRANTID AGENCY COUNTRY
089703 Wellcome Trust United Kingdom
BB/F019394/1 Biotechnology and Biological Sciences Research Council United Kingdom
BB/F022441/1 Biotechnology and Biological Sciences Research Council United Kingdom
CZB/4/505 Chief Scientist Office United Kingdom
ETM/55 Chief Scientist Office United Kingdom
MR/K026992/1 Medical Research Council United Kingdom
Biotechnology and Biological Sciences Research Council United Kingdom
Medical Research Council United Kingdom
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC3905224 NLM