Integrative Multi-omics Analysis of Childhood Aggressive Behavior

• Published in: Behavior genetics Vol. 53; no. 2; pp. 101 - 117
• Main Authors: Hagenbeek, Fiona A., van Dongen, Jenny, Pool, René, Roetman, Peter J., Harms, Amy C., Hottenga, Jouke Jan, Kluft, Cornelis, Colins, Olivier F., van Beijsterveldt, Catharina E. M., Fanos, Vassilios, Ehli, Erik A., Hankemeier, Thomas, Vermeiren, Robert R. J. M., Bartels, Meike, Déjean, Sébastien, Boomsma, Dorret I.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2023; Springer Nature B.V; Springer Verlag
• Subjects: Aggression; Aggressive behavior; Aggressiveness; Amino acids; Attention deficit hyperactivity disorder; Autism; Autism Spectrum Disorder; Behavioral Science and Psychology; Biological analysis; Biological markers; Biology; Biomarkers; Carcinogens; Childhood; Children; Clinical Psychology; Cognition; Deoxyribonucleic acid; DNA; DNA methylation; Health Psychology; Humans; Inflammation; Intelligence; Mathematics; Metabolites; Multiomics; Original Research; Polygenic inheritance; Psychology; Public Health; Risk factors; Smoking; Statistics; DNA methylation; Metabolomics; Childhood aggression; Genetic nurturing; Multi-omics; Polygenic scores
• ISSN: 0001-8244; 1573-3297
• DOI: 10.1007/s10519-022-10126-7

This study introduces and illustrates the potential of an integrated multi-omics approach in investigating the underlying biology of complex traits such as childhood aggressive behavior. In 645 twins (cases = 42%), we trained single- and integrative multi-omics models to identify biomarkers for subclinical aggression and investigated the connections among these biomarkers. Our data comprised transmitted and two non-transmitted polygenic scores (PGSs) for 15 traits, 78,772 CpGs, and 90 metabolites. The single-omics models selected 31 PGSs, 1614 CpGs, and 90 metabolites, and the multi-omics model comprised 44 PGSs, 746 CpGs, and 90 metabolites. The predictive accuracy for these models in the test ( N  = 277, cases = 42%) and independent clinical data ( N  = 142, cases = 45%) ranged from 43 to 57%. We observed strong connections between DNA methylation, amino acids, and parental non-transmitted PGSs for ADHD, Autism Spectrum Disorder, intelligence, smoking initiation, and self-reported health. Aggression-related omics traits link to known and novel risk factors, including inflammation, carcinogens, and smoking.