|
PMID |
|
|
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 |
|
|
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 |
|
|