Integrative multi-omics analysis of childhood aggressive behavior

Abstract

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. Using multivariate statistical methods, we integrated 45 polygenic scores (PGSs) based on genome-wide SNP data, 78,772 CpGs, and 90 metabolites for 645 twins (cases=42.0%, controls=58.0%). The single-omics models selected 31 PGSs, 1614 CpGs, and 90 metabolites, and the multi-omics biomarker panel comprised 44 PGSs, 746 CpGs, and 90 metabolites. The predictive accuracy in the test (N=277, cases=42.2%, controls=57.8%) and validation data (N=142 participants from a clinical cohort, cases=45.1%, controls=54.9%) ranged from 43.0% to 57.0% for the single- and multi-omics models. The average correlations across omics layers of omics traits selected for aggression in single-omics models ranged from 0.18 to 0.28. In the multi-omics model higher correlations were found and we describe five sets of correlational patterns with high absolute correlations (|r| ≥ 0.60) of aggression-related omics traits selected into the multi-omics model, providing novel biological insights.

Integrative multi-omics analysis of genomic, epigenomic, and metabolomics data leads to new insights for Attention-Deficit/Hyperactivity Disorder

“…All analyses were performed in R (version 4.1.1) mainly using the mixOmics package (version 6.16.3; Rohart et al, 2017). The analytical design consisted of three steps as previously described in Hagenbeek et al (2022; under review): 1) three single-omics analyses; 2) two sets of pairwise cross-omics analyses; and 3) a multi-omics analysis ( Figure 1 ). The twin sample was randomly split at twin pair level to create two subsets: 70% of the data were used for model training (training data), and 30% of the data for model testing (test data; Table 2 ).…”

“…Participants were selected from the Young Netherlands Twin Register (van Beijsterveldt et al, 2013), and children referred to a youth psychiatry clinic (LUMC-Curium, the Netherlands), as part of the ACTION (Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies) Biomarker Study (Barters et al, 2018;Hagenbeek, Roetman, et al, 2020).…”

Differences in well-being

“…To learn more about multi-omics, Wörheide et al (2021) and Subramanian et al (2020) provide helpful overviews and different applications of this approach within the domain of mental ill-being, e.g., for aggressive behavior and psychiatric disorders, can be found (Hagenbeek et al, 2021;Korologou-Linden et al, 2021).…”