Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.
GWAS
cognitive ability
educational attainment
genetic correlation
pathways
pleiotropy
schizophrenia
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
01 08 2019
01 08 2019
Historique:
received:
23
01
2019
accepted:
12
06
2019
entrez:
3
8
2019
pubmed:
3
8
2019
medline:
17
3
2020
Statut:
ppublish
Résumé
Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected ("concordant") direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive ("discordant") relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10
Identifiants
pubmed: 31374203
pii: S0002-9297(19)30237-X
doi: 10.1016/j.ajhg.2019.06.012
pmc: PMC6699140
pii:
doi:
Types de publication
Journal Article
Meta-Analysis
Langues
eng
Sous-ensembles de citation
IM
Pagination
334-350Subventions
Organisme : NIMH NIH HHS
ID : R01 MH117646
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085018
Pays : United States
Organisme : NIMH NIH HHS
ID : L30 MH104879
Pays : United States
Organisme : Medical Research Council
ID : G0600237
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH100141
Pays : United States
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/F019394/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0100594
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/F022441/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0901461
Pays : United Kingdom
Informations de copyright
Copyright © 2019. Published by Elsevier Inc.
Références
Nat Commun. 2018 May 8;9(1):1825
pubmed: 29739930
Neuron. 2017 Jun 7;94(5):969-977
pubmed: 28595053
Schizophr Bull. 2006 Jan;32(1):179-94
pubmed: 16166612
Cell. 2014 Jul 17;158(2):263-276
pubmed: 24998929
Mol Psychiatry. 2017 Dec;22(12):1659-1663
pubmed: 28322284
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Mol Psychiatry. 2015 Feb;20(2):183-92
pubmed: 25644384
Am J Hum Genet. 2018 Jun 7;102(6):1169-1184
pubmed: 29805045
Nat Genet. 2015 Jun;47(6):582-8
pubmed: 25961944
Nat Genet. 2018 Feb;50(2):229-237
pubmed: 29292387
Sci Rep. 2017 Sep 29;7(1):12460
pubmed: 28963561
Neuron. 2014 Jul 16;83(2):266-282
pubmed: 25033177
Mol Psychiatry. 2016 Nov;21(11):1624-1632
pubmed: 26809841
Neuropsychology. 1998 Jul;12(3):426-45
pubmed: 9673998
JAMA Psychiatry. 2018 Sep 1;75(9):929-939
pubmed: 30046827
Nature. 2012 Apr 04;485(7397):242-5
pubmed: 22495311
Mol Psychiatry. 2014 Jun;19(6):652-8
pubmed: 24776741
Curr Mol Med. 2015;15(2):119-28
pubmed: 25732151
Nat Genet. 2017 Aug;49(8):1167-1173
pubmed: 28650482
PLoS Comput Biol. 2015 Apr 17;11(4):e1004219
pubmed: 25885710
Mol Psychiatry. 2014 Feb;19(2):168-74
pubmed: 24342994
Cell Res. 2015 Sep;25(9):993-4
pubmed: 26183066
Science. 2018 Jun 22;360(6395):
pubmed: 29930110
Mol Psychiatry. 2011 Mar;16(3):286-92
pubmed: 20157312
Nature. 2011 Oct 26;478(7370):483-9
pubmed: 22031440
J Clin Exp Neuropsychol. 2006 Feb;28(2):270-82
pubmed: 16484098
Schizophr Res. 2016 Dec;178(1-3):104-106
pubmed: 27595554
PLoS One. 2018 Mar 1;13(3):e0193256
pubmed: 29494641
Biol Psychiatry. 2016 Aug 15;80(4):266-273
pubmed: 26476593
Nat Genet. 2015 Nov;47(11):1236-41
pubmed: 26414676
Am J Hum Genet. 2012 May 4;90(5):821-35
pubmed: 22560090
Nat Genet. 2015 Mar;47(3):291-5
pubmed: 25642630
Nat Commun. 2018 May 29;9(1):2098
pubmed: 29844566
Am J Hum Genet. 2017 Dec 7;101(6):939-964
pubmed: 29220677
JAMA Psychiatry. 2017 Oct 1;74(10):1065-1075
pubmed: 28746715
Mol Psychiatry. 2018 Dec;23(12):2347-2362
pubmed: 29321673
Neuropsychology. 2009 May;23(3):315-36
pubmed: 19413446
Annu Rev Genomics Hum Genet. 2013;14:301-23
pubmed: 23875801
Transl Psychiatry. 2014 Jan 07;4:e341
pubmed: 24399044
Mol Psychiatry. 2017 Mar;22(3):336-345
pubmed: 28093568
Nature. 2014 Feb 13;506(7487):185-90
pubmed: 24463508
Psychol Med. 2008 Aug;38(8):1133-40
pubmed: 17988422
Nature. 2014 Jul 24;511(7510):421-7
pubmed: 25056061
Am J Med Genet B Neuropsychiatr Genet. 2007 Mar 5;144B(2):242-9
pubmed: 17034022
Schizophr Bull. 2017 May 1;43(3):654-664
pubmed: 27338279
World Psychiatry. 2008 Feb;7(1):22-8
pubmed: 18458774
Sci Rep. 2017 Nov 16;7(1):15736
pubmed: 29147026
Nat Neurosci. 2015 Jul;18(7):953-5
pubmed: 26053403
Schizophr Res. 2009 Feb;107(2-3):262-6
pubmed: 19042105
Nat Commun. 2018 Aug 6;9(1):3078
pubmed: 30082721
Nat Neurosci. 2016 Nov;19(11):1477-1488
pubmed: 27694995
Nat Neurosci. 2017 Aug;20(8):1062-1073
pubmed: 28671691
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
Cereb Cortex. 2018 Jun 1;28(6):2192-2206
pubmed: 29668850
Nat Neurosci. 2016 Nov;19(11):1442-1453
pubmed: 27668389
Nat Commun. 2017 Nov 28;8(1):1826
pubmed: 29184056
Am J Psychiatry. 2010 Feb;167(2):160-9
pubmed: 20048021
Nat Commun. 2016 Nov 08;7:13316
pubmed: 27824329
Nat Genet. 2017 Jul;49(7):1107-1112
pubmed: 28530673
Mol Psychiatry. 2016 Jun;21(6):758-67
pubmed: 27046643
Nat Neurosci. 2015 Feb;18(2):199-209
pubmed: 25599223
Am J Psychiatry. 2000 Apr;157(4):549-59
pubmed: 10739413
Cell Rep. 2017 Nov 28;21(9):2597-2613
pubmed: 29186694
Nat Genet. 2018 Jul;50(7):956-967
pubmed: 29955180
Bioinformatics. 2010 Sep 1;26(17):2190-1
pubmed: 20616382
Nature. 2016 Feb 11;530(7589):177-83
pubmed: 26814963
Am J Hum Genet. 2017 Jun 1;100(6):885-894
pubmed: 28552197
Nat Genet. 2018 Mar;50(3):381-389
pubmed: 29483656
Biol Psychiatry. 2006 May 1;59(9):863-71
pubmed: 16325151
Mol Psychiatry. 2013 Feb;18(2):190-4
pubmed: 22472877
Nat Genet. 2018 Aug;50(8):1112-1121
pubmed: 30038396
Bioinformatics. 2005 Jan 15;21(2):263-5
pubmed: 15297300
Nature. 2016 May 11;533(7604):539-42
pubmed: 27225129
Nat Genet. 2018 Jul;50(7):912-919
pubmed: 29942086
Nat Genet. 2018 May;50(5):737-745
pubmed: 29700474
Am J Psychiatry. 2003 Apr;160(4):636-45
pubmed: 12668349
Nat Genet. 2015 Sep;47(9):1091-8
pubmed: 26258848
Mol Psychiatry. 2019 Feb;24(2):169-181
pubmed: 29326435
Cell Rep. 2017 Oct 17;21(3):679-691
pubmed: 29045836
Mol Cell Neurosci. 2018 Oct;92:50-66
pubmed: 29981480
Prog Neurobiol. 2012 Oct;99(1):81-91
pubmed: 22813947
Science. 2015 May 8;348(6235):648-60
pubmed: 25954001
Arch Gen Psychiatry. 2005 Dec;62(12):1297-304
pubmed: 16330717
Curr Opin Psychol. 2019 Jun;27:25-30
pubmed: 30110665
J Med Genet. 1996 Jun;33(6):458-64
pubmed: 8782044
Dev Psychopathol. 1999 Summer;11(3):487-508
pubmed: 10532621
Mol Genet Metab. 2016 Aug;118(4):296-303
pubmed: 27344355
Soc Psychiatry Psychiatr Epidemiol. 2009 Nov;44(11):999-1004
pubmed: 19294321
Am J Psychiatry. 2002 Dec;159(12):2027-35
pubmed: 12450952