Integrative multi-omics analysis of genomic, epigenomic, and metabolomics data leads to new insights for Attention-Deficit/Hyperactivity Disorder.
ADHD
DNA methylation
genetic nurture
metabolites
multi-omics
polygenic scores
Journal
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
ISSN: 1552-485X
Titre abrégé: Am J Med Genet B Neuropsychiatr Genet
Pays: United States
ID NLM: 101235742
Informations de publication
Date de publication:
03 Aug 2023
03 Aug 2023
Historique:
revised:
13
06
2023
received:
22
07
2022
accepted:
11
07
2023
pubmed:
3
8
2023
medline:
3
8
2023
entrez:
3
8
2023
Statut:
aheadofprint
Résumé
The evolving field of multi-omics combines data and provides methods for simultaneous analysis across several omics levels. Here, we integrated genomics (transmitted and non-transmitted polygenic scores [PGSs]), epigenomics, and metabolomics data in a multi-omics framework to identify biomarkers for Attention-Deficit/Hyperactivity Disorder (ADHD) and investigated the connections among the three omics levels. We first trained single- and next multi-omics models to differentiate between cases and controls in 596 twins (cases = 14.8%) from the Netherlands Twin Register (NTR) demonstrating reasonable in-sample prediction through cross-validation. The multi-omics model selected 30 PGSs, 143 CpGs, and 90 metabolites. We confirmed previous associations of ADHD with glucocorticoid exposure and the transmembrane protein family TMEM, show that the DNA methylation of the MAD1L1 gene associated with ADHD has a relation with parental smoking behavior, and present novel findings including associations between indirect genetic effects and CpGs of the STAP2 gene. However, out-of-sample prediction in NTR participants (N = 258, cases = 14.3%) and in a clinical sample (N = 145, cases = 51%) did not perform well (range misclassification was [0.40, 0.57]). The results highlighted connections between omics levels, with the strongest connections between non-transmitted PGSs, CpGs, and amino acid levels and show that multi-omics designs considering interrelated omics levels can help unravel the complex biology underlying ADHD.
Identifiants
pubmed: 37534875
doi: 10.1002/ajmg.b.32955
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e32955Subventions
Organisme : European Research Council
Pays : International
Organisme : ZonMw
ID : 911-09-032
Pays : Netherlands
Organisme : ZonMw
ID : 912-10-020
Pays : Netherlands
Informations de copyright
© 2023 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.
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