Transcriptomic risk scores for attention deficit/hyperactivity disorder.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
07
02
2023
accepted:
21
07
2023
revised:
17
07
2023
medline:
2
11
2023
pubmed:
4
8
2023
entrez:
3
8
2023
Statut:
ppublish
Résumé
Attention deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. We performed a transcriptome-wide association study (TWAS) using the latest genome-wide association study (GWAS) meta-analysis, in 38,691 individuals with ADHD and 186,843 controls, and 14 gene-expression reference panels across multiple brain tissues and whole blood. Based on TWAS results, we selected subsets of genes and constructed transcriptomic risk scores (TRSs) for the disorder in peripheral blood mononuclear cells of individuals with ADHD and controls. We found evidence of association between ADHD and TRSs constructed using expression profiles from multiple brain areas, with individuals with ADHD carrying a higher burden of TRSs than controls. TRSs were uncorrelated with the polygenic risk score (PRS) for ADHD and, in combination with PRS, improved significantly the proportion of variance explained over the PRS-only model. These results support the complementary predictive potential of genetic and transcriptomic profiles in blood and underscore the potential utility of gene expression for risk prediction and deeper insight in molecular mechanisms underlying ADHD.
Identifiants
pubmed: 37537283
doi: 10.1038/s41380-023-02200-1
pii: 10.1038/s41380-023-02200-1
pmc: PMC10618083
doi:
Types de publication
Meta-Analysis
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3493-3502Subventions
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : CP22/00026
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : P19/01224
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : PI20/00041
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : PI22/00464
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : FI18/00285
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : CP22/00128
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF20OC0065561
Organisme : Lundbeckfonden (Lundbeck Foundation)
ID : R344-2020-1060
Informations de copyright
© 2023. The Author(s).
Références
BMC Med Genomics. 2020 Oct 28;13(1):160
pubmed: 33115496
Nat Rev Mol Cell Biol. 2021 Feb;22(2):96-118
pubmed: 33353982
Genet Epidemiol. 2009 Nov;33(7):559-68
pubmed: 19217024
Am J Hum Genet. 2022 May 5;109(5):825-837
pubmed: 35523146
Bioinformatics. 2016 May 15;32(10):1493-501
pubmed: 26773131
Eur Neuropsychopharmacol. 2020 Dec;41:160-166
pubmed: 33221139
J Neurosci. 2016 Nov 9;36(45):11411-11417
pubmed: 27911743
Nat Genet. 2012 Oct;44(10):1084-9
pubmed: 22941192
Neuromolecular Med. 2019 Jun;21(2):97-109
pubmed: 30963386
Neurol Genet. 2020 Sep 30;6(6):e517
pubmed: 33134515
JIMD Rep. 2018;38:23-31
pubmed: 28456886
Nat Commun. 2018 May 8;9(1):1825
pubmed: 29739930
Mol Psychiatry. 2018 Aug;23(8):1787-1793
pubmed: 29180674
Gigascience. 2019 Jul 1;8(7):
pubmed: 31307061
Nat Genet. 2019 Mar;51(3):431-444
pubmed: 30804558
Nat Genet. 2017 Oct;49(10):1517-1521
pubmed: 28805827
Neuropsychopharmacology. 2019 Apr;44(5):890-897
pubmed: 30568281
J Affect Disord. 2012 May;138(3):479-84
pubmed: 22370065
PLoS Genet. 2011 Feb 03;7(2):e1002003
pubmed: 21304890
Am J Psychiatry. 2019 Jul 1;176(7):531-542
pubmed: 31014101
Psychol Med. 2014 Jul;44(10):2223-9
pubmed: 24107258
J Glob Health. 2021 Feb 11;11:04009
pubmed: 33692893
Gigascience. 2015 Feb 25;4:7
pubmed: 25722852
J Bone Miner Res. 2017 Aug;32(8):1651-1658
pubmed: 28425624
Neurochem Int. 2021 Oct;149:105140
pubmed: 34298078
J Am Acad Child Adolesc Psychiatry. 2021 Oct;60(10):1234-1277
pubmed: 33548493
Nat Genet. 2019 Jan;51(1):63-75
pubmed: 30478444
Sci Rep. 2017 Jul 14;7(1):5407
pubmed: 28710364
Genetics. 2015 Jul;200(3):719-36
pubmed: 25948564
Transl Psychiatry. 2022 Sep 24;12(1):409
pubmed: 36153331
Science. 2020 Sep 11;369(6509):1318-1330
pubmed: 32913098
Front Genet. 2019 Aug 09;10:733
pubmed: 31447886
Bioinformatics. 2005 Mar;21(6):754-64
pubmed: 15479708
Eur Neuropsychopharmacol. 2021 Mar;44:1-13
pubmed: 33495110
Bioinformatics. 2009 Feb 1;25(3):415-6
pubmed: 19106121
Transl Psychiatry. 2016 Aug 30;6(8):e879
pubmed: 27576168
Psychiatry Res. 2019 Dec;282:112639
pubmed: 31685286
Bioinformatics. 2010 Oct 1;26(19):2363-7
pubmed: 20688976
Dev Cell. 2012 Aug 14;23(2):356-70
pubmed: 22898779
Nucleic Acids Res. 2020 Jan 8;48(D1):D807-D816
pubmed: 31691819
Nat Commun. 2017 Nov 28;8(1):1826
pubmed: 29184056
Psychiatry Res. 2018 Dec;270:544-546
pubmed: 30343239
Science. 2018 Dec 14;362(6420):
pubmed: 30545857
Nat Genet. 2018 Apr;50(4):538-548
pubmed: 29632383
Nat Commun. 2019 Jul 24;10(1):3300
pubmed: 31341166
Nat Genet. 2023 Feb;55(2):198-208
pubmed: 36702997
Stem Cell Reports. 2018 Apr 10;10(4):1237-1250
pubmed: 29526736
Neuropsychopharmacology. 2021 Dec;46(13):2304-2311
pubmed: 34588609
Mol Psychiatry. 2020 Aug;25(8):1809-1821
pubmed: 29934545
Nat Genet. 2020 Nov;52(11):1239-1246
pubmed: 33020666
Behav Brain Res. 2019 May 17;364:183-192
pubmed: 30738099
Nat Commun. 2019 Apr 16;10(1):1776
pubmed: 30992449
Nat Commun. 2019 Oct 1;10(1):4450
pubmed: 31575856
Br J Psychiatry. 2016 Sep;209(3):202-8
pubmed: 27151072
Brain Sci. 2019 Sep 27;9(10):
pubmed: 31569608
Hum Mol Genet. 2021 May 17;30(8):727-738
pubmed: 33611520
Neuropsychopharmacology. 2020 Sep;45(10):1617-1626
pubmed: 32279069
Brain Sci. 2019 Oct 22;9(10):
pubmed: 31652596
Nat Rev Dis Primers. 2015 Aug 06;1:15020
pubmed: 27189265
Genet Epidemiol. 2012 Apr;36(3):214-24
pubmed: 22714935
J Child Psychol Psychiatry. 2021 Oct;62(10):1202-1219
pubmed: 33748971
Prog Neuropsychopharmacol Biol Psychiatry. 2020 Mar 2;98:109815
pubmed: 31715283