eprintid: 10203221
rev_number: 7
eprint_status: archive
userid: 699
dir: disk0/10/20/32/21
datestamp: 2025-01-13 11:53:02
lastmod: 2025-01-13 11:53:02
status_changed: 2025-01-13 11:53:02
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Askelund, Adrian Dahl
creators_name: Hegemann, Laura
creators_name: Allegrini, Andrea G
creators_name: Corfield, Elizabeth C
creators_name: Ask, Helga
creators_name: Davies, Neil M
creators_name: Andreassen, Ole A
creators_name: Havdahl, Alexandra
creators_name: Hannigan, Laurie J
title: The genetic architecture of differentiating behavioral and emotional problems in early life
ispublished: inpress
divisions: UCL
divisions: B02
divisions: C07
divisions: D79
divisions: FH7
keywords: differentiation; behavioral problems; emotional problems; attention-deficit/hyperactivity disorder; genomic structural equation modeling; trio polygenic score.
note: © The Author(s), 2025. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/
abstract: Background:
Early in life, behavioral and cognitive traits associated with risk for developing a psychiatric condition are broad and undifferentiated. As children develop, these traits differentiate into characteristic clusters of symptoms and behaviors that ultimately form the basis of diagnostic categories. Understanding this differentiation process – in the context of genetic risk for psychiatric conditions, which is highly generalized – can improve early detection and intervention.//

Methods:
We modeled the differentiation of behavioral and emotional problems from age 1.5-5 years (behavioral problems – emotional problems = differentiation score) in a pre-registered study of ∼79,000 children from the population-based Norwegian Mother, Father, and Child Cohort Study. We used genomic structural equation modeling to identify genetic signal in differentiation and total problems, investigating their links with 11 psychiatric and neurodevelopmental conditions. We examined associations of polygenic scores (PGS) with both outcomes and assessed the relative contributions of direct and indirect genetic effects in ∼33,000 family trios.//

Results:
Differentiation was primarily genetically correlated with psychiatric conditions via a “neurodevelopmental” factor. Total problems were primarily associated with the “neurodevelopmental” factor and “p”-factor. PGS analyses revealed an association between liability to ADHD and differentiation (β=0.11 [0.10,0.12]), and a weaker association with total problems (β=0.06 [0.04,0.07]). Trio-PGS analyses showed predominantly direct genetic effects on both outcomes.//

Conclusions:
We uncovered genomic signal in the differentiation process, mostly related to common variants associated with neurodevelopmental conditions. Investigating the differentiation of early life behavioral and emotional problems may enhance our understanding of the developmental emergence of different psychiatric and neurodevelopmental conditions.
date: 2025-01-09
date_type: published
publisher: Elsevier BV
official_url: https://doi.org/10.1016/j.biopsych.2024.12.021
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2352103
doi: 10.1016/j.biopsych.2024.12.021
lyricists_name: Davies, Neil
lyricists_id: NDAVI50
actors_name: Davies, Neil
actors_id: NDAVI50
actors_role: owner
full_text_status: public
publication: Biological Psychiatry
issn: 0006-3223
citation:        Askelund, Adrian Dahl;    Hegemann, Laura;    Allegrini, Andrea G;    Corfield, Elizabeth C;    Ask, Helga;    Davies, Neil M;    Andreassen, Ole A;         ... Hannigan, Laurie J; + view all <#>        Askelund, Adrian Dahl;  Hegemann, Laura;  Allegrini, Andrea G;  Corfield, Elizabeth C;  Ask, Helga;  Davies, Neil M;  Andreassen, Ole A;  Havdahl, Alexandra;  Hannigan, Laurie J;   - view fewer <#>    (2025)    The genetic architecture of differentiating behavioral and emotional problems in early life.                   Biological Psychiatry        10.1016/j.biopsych.2024.12.021 <https://doi.org/10.1016/j.biopsych.2024.12.021>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10203221/1/PIIS0006322325000228.pdf