A family-based study of genetic and epigenetic effects across multiple neurocognitive, motor, social-cognitive and social-behavioral functions.
Cognitive functions
Endophenotype
GWAS
Neurodevelopment
Parent-of-origin effect
Journal
Behavioral and brain functions : BBF
ISSN: 1744-9081
Titre abrégé: Behav Brain Funct
Pays: England
ID NLM: 101245751
Informations de publication
Date de publication:
01 Dec 2022
01 Dec 2022
Historique:
received:
24
02
2022
accepted:
09
09
2022
entrez:
2
12
2022
pubmed:
3
12
2022
medline:
6
12
2022
Statut:
epublish
Résumé
Many psychiatric and neurodevelopmental disorders are known to be heritable, but studies trying to elucidate the genetic architecture of such traits often lag behind studies of somatic traits and diseases. The reasons as to why relatively few genome-wide significant associations have been reported for such traits have to do with the sample sizes needed for the detection of small effects, the difficulty in defining and characterizing the phenotypes, partially due to overlaps in affected underlying domains (which is especially true for cognitive phenotypes), and the complex genetic architectures of the phenotypes, which are not wholly captured in traditional case-control GWAS designs. We aimed to tackle the last two issues by performing GWASs of eight quantitative neurocognitive, motor, social-cognitive and social-behavioral traits, which may be considered endophenotypes for a variety of psychiatric and neurodevelopmental conditions, and for which we employed models capturing both general genetic association and parent-of-origin effects, in a family-based sample comprising 402 children and their parents (mostly family trios). We identified 48 genome-wide significant associations across several traits, of which 3 also survived our strict study-wide quality criteria. We additionally performed a functional annotation of implicated genes, as most of the 48 associations were with variants within protein-coding genes. In total, our study highlighted associations with five genes (TGM3, CACNB4, ANKS1B, CSMD1 and SYNE1) associated with measures of working memory, processing speed and social behavior. Our results thus identify novel associations, including previously unreported parent-of-origin associations with relevant genes, and our top results illustrate new potential gene → endophenotype → disorder pathways.
Identifiants
pubmed: 36457050
doi: 10.1186/s12993-022-00198-0
pii: 10.1186/s12993-022-00198-0
pmc: PMC9714039
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
14Informations de copyright
© 2022. The Author(s).
Références
BMC Genomics. 2016 Jun 23;17 Suppl 2:444
pubmed: 27357693
Am J Hum Genet. 1998 Apr;62(4):969-78
pubmed: 9529360
Transl Psychiatry. 2020 Jul 5;10(1):215
pubmed: 32624584
Bioinformatics. 2019 Nov 1;35(22):4851-4853
pubmed: 31233103
J Neurodev Disord. 2013 Oct 05;5(1):30
pubmed: 24093601
Schizophr Res. 2014 Apr;154(1-3):42-7
pubmed: 24630139
Cell. 2016 Nov 17;167(5):1398-1414.e24
pubmed: 27863251
Nat Commun. 2019 Aug 6;10(1):3529
pubmed: 31388001
Nat Genet. 2007 Jan;39(1):80-5
pubmed: 17159980
Curr Psychiatry Rep. 2014 Nov;16(11):498
pubmed: 25234074
Nat Rev Genet. 2010 Jun;11(6):446-50
pubmed: 20479774
Pharmacogenomics. 2019 Jun;20(9):669-684
pubmed: 31250731
Hum Mol Genet. 2014 Jun 1;23(11):3045-53
pubmed: 24403052
Psychophysiology. 2014 Dec;51(12):1339-47
pubmed: 25387720
J Neurodev Disord. 2016 Jun 14;8:24
pubmed: 27307794
Physiol Rep. 2013 Dec 17;1(7):e00188
pubmed: 24744865
Neurobiol Dis. 2010 Jul;39(1):13-20
pubmed: 20304067
Biomark Med. 2017 Sep;11(9):769-780
pubmed: 28891303
Nat Commun. 2016 Nov 16;7:13490
pubmed: 27848971
Mol Autism. 2010 Apr 08;1(1):8
pubmed: 20678250
Curr Protoc Bioinformatics. 2016 Jun 20;54:1.30.1-1.30.33
pubmed: 27322403
PLoS One. 2015 Apr 21;10(4):e0120758
pubmed: 25898129
Eur J Hum Genet. 2017 Feb;25(2):234-239
pubmed: 27876814
Am J Med Genet. 2001 Jan 8;105(1):42-4
pubmed: 11424994
Schizophr Bull. 2016 May;42(3):832-42
pubmed: 26678674
Mol Psychiatry. 2018 Mar;23(3):533-543
pubmed: 28696432
Science. 2002 Apr 26;296(5568):692-5
pubmed: 11976442
Nat Genet. 2017 Jan;49(1):131-138
pubmed: 27918535
J Autism Dev Disord. 2003 Aug;33(4):427-33
pubmed: 12959421
Mol Cancer. 2013 Dec 01;12(1):151
pubmed: 24289313
Biol Psychiatry. 2011 Jul 1;70(1):35-42
pubmed: 21439553
Nat Genet. 2011 Sep 18;43(10):969-76
pubmed: 21926974
Nature. 2009 Dec 17;462(7275):868-74
pubmed: 20016592
Nat Rev Genet. 2008 Apr;9(4):255-66
pubmed: 18319743
Cerebellum. 2019 Aug;18(4):731-737
pubmed: 31049853
Int J Alzheimers Dis. 2011 Feb 16;2011:865432
pubmed: 21350675
Am J Hum Genet. 2002 Dec;71(6):1330-41
pubmed: 12454799
BMC Neurosci. 2020 Jul 7;21(1):30
pubmed: 32635940
Alzheimer Dis Assoc Disord. 2014 Jul-Sep;28(3):226-33
pubmed: 24731980
Soc Neurosci. 2006;1(3-4):412-25
pubmed: 18633802
Atten Defic Hyperact Disord. 2011 Sep;3(3):291-9
pubmed: 21779842
Nat Protoc. 2010 Sep;5(9):1564-73
pubmed: 21085122
J Child Psychol Psychiatry. 2016 Apr;57(4):446-56
pubmed: 26577292
Genet Epidemiol. 2011 Jan;35(1):19-45
pubmed: 21181895
Neuroscience. 2011 Dec 1;197:121-31
pubmed: 21925573
Nat Genet. 2002 Jan;30(1):97-101
pubmed: 11731797
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
Twin Res Hum Genet. 2011 Apr;14(2):119-28
pubmed: 21425893
Am J Med Genet C Semin Med Genet. 2010 Aug 15;154C(3):365-76
pubmed: 20803659
Am J Med Genet. 2000 Summer;97(2):136-46
pubmed: 11180221
Autism Res. 2020 Mar;13(3):369-381
pubmed: 31577390
Neurosci Bull. 2017 Apr;33(2):183-193
pubmed: 28213805
J Bioenerg Biomembr. 2003 Dec;35(6):599-620
pubmed: 15000522
Trends Mol Med. 2003 Nov;9(11):490-5
pubmed: 14604827
JAMA Psychiatry. 2018 Aug 1;75(8):844-852
pubmed: 29926086
Acta Genet Med Gemellol (Roma). 1980;29(2):127-36
pubmed: 7196128
J Sports Sci Med. 2009 Jun 01;8(2):154-68
pubmed: 24149522
Nat Genet. 2011 Jun;43(6):585-9
pubmed: 21572417
Genes Brain Behav. 2014 Apr;13(4):418-29
pubmed: 24571439
Lancet Psychiatry. 2017 May;4(5):400-408
pubmed: 28344044
Schizophr Bull. 2018 Aug 20;44(5):958-965
pubmed: 29982775
Sci Rep. 2016 Jun 23;6:28496
pubmed: 27333805
Nat Rev Genet. 2013 Sep;14(9):609-17
pubmed: 23917626
Prog Neurobiol. 2015 Nov;134:36-54
pubmed: 26386135
Lancet. 2013 Apr 20;381(9875):1371-1379
pubmed: 23453885
Curr Dir Psychol Sci. 2006 Oct;15(5):217-221
pubmed: 19009045
BMC Bioinformatics. 2012 Jun 27;13:149
pubmed: 22738121
Child Dev. 2009 Jul-Aug;80(4):1097-117
pubmed: 19630896
Am J Hum Genet. 2007 Sep;81(3):559-75
pubmed: 17701901
Am J Psychiatry. 2007 Apr;164(4):656-62
pubmed: 17403980
Arch Gen Psychiatry. 2003 May;60(5):524-30
pubmed: 12742874
PLoS Genet. 2020 Mar 16;16(3):e1008625
pubmed: 32176688
J Neurodev Disord. 2014 Jan 17;6(1):1
pubmed: 24433325
Bioinformatics. 2010 Sep 15;26(18):2336-7
pubmed: 20634204
Commun Biol. 2019 Jan 18;2:28
pubmed: 30675526
Am J Hum Genet. 2000 Jan;66(1):279-92
pubmed: 10631157
BMC Psychiatry. 2015 Oct 02;15:233
pubmed: 26432691
Biochim Biophys Acta. 2014 Mar;1839(3):169-77
pubmed: 24345612
Trends Neurosci. 2020 Aug;43(8):608-621
pubmed: 32507511
Am J Psychiatry. 2003 Apr;160(4):636-45
pubmed: 12668349
Nat Rev Genet. 2018 Mar;19(3):148-159
pubmed: 29335645
Am J Psychiatry. 2015 Mar 1;172(3):266-75
pubmed: 25727539
J Child Psychol Psychiatry. 2008 Sep;49(9):950-7
pubmed: 18665883
Mol Autism. 2013 Sep 18;4(1):34
pubmed: 24047820
Nature. 2009 Oct 8;461(7265):747-53
pubmed: 19812666
Nature. 2017 Jul 20;547(7663):340-344
pubmed: 28700580
Schizophr Bull. 2017 Jul 1;43(4):788-800
pubmed: 27872257
Cell. 2014 Jan 16;156(1-2):332-42
pubmed: 24439386
EMBO J. 2003 Aug 15;22(16):4121-31
pubmed: 12912911
Mol Psychiatry. 2010 Nov;15(11):1112-20
pubmed: 19488046
Front Psychiatry. 2015 Aug 03;6:105
pubmed: 26283973
Am J Psychiatry. 2000 Feb;157(2):275-7
pubmed: 10671401
Schizophr Bull. 2019 Oct 24;45(6):1218-1230
pubmed: 30852621