Schlag, Fenja;
Allegrini, Andrea G;
Buitelaar, Jan;
Verhoef, Ellen;
van Donkelaar, Marjolein;
Plomin, Robert;
Rimfeld, Kaili;
... St Pourcain, Beate; + view all
(2022)
Polygenic risk for mental disorder reveals distinct association profiles across social behaviour in the general population.
Molecular Psychiatry
, 27
pp. 1588-1598.
10.1038/s41380-021-01419-0.
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Abstract
Many mental health conditions present a spectrum of social difficulties that overlaps with social behaviour in the general population including shared but little characterised genetic links. Here, we systematically investigate heterogeneity in shared genetic liabilities with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), bipolar disorder (BP), major depression (MD) and schizophrenia across a spectrum of different social symptoms. Longitudinally assessed low-prosociality and peer-problem scores in two UK population-based cohorts (4–17 years; parent- and teacher-reports; Avon Longitudinal Study of Parents and Children(ALSPAC): N ≤ 6,174; Twins Early Development Study(TEDS): N ≤ 7,112) were regressed on polygenic risk scores for disorder, as informed by genome-wide summary statistics from large consortia, using negative binomial regression models. Across ALSPAC and TEDS, we replicated univariate polygenic associations between social behaviour and risk for ADHD, MD and schizophrenia. Modelling variation in univariate genetic effects jointly using random-effect meta-regression revealed evidence for polygenic links between social behaviour and ADHD, ASD, MD, and schizophrenia risk, but not BP. Differences in age, reporter and social trait captured 45–88% in univariate effect variation. Cross-disorder adjusted analyses demonstrated that age-related heterogeneity in univariate effects is shared across mental health conditions, while reporter- and social trait-specific heterogeneity captures disorder-specific profiles. In particular, ADHD, MD, and ASD polygenic risk were more strongly linked to peer problems than low prosociality, while schizophrenia was associated with low prosociality only. The identified association profiles suggest differences in the social genetic architecture across mental disorders when investigating polygenic overlap with population-based social symptoms spanning 13 years of child and adolescent development.
| Type: | Article |
|---|---|
| Title: | Polygenic risk for mental disorder reveals distinct association profiles across social behaviour in the general population |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41380-021-01419-0 |
| Publisher version: | https://doi.org/10.1038/s41380-021-01419-0 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Neurosciences, Psychiatry, Neurosciences & Neurology, DIFFICULTIES QUESTIONNAIRE, PSYCHIATRIC-DISORDERS, PROSOCIAL BEHAVIOR, SCHIZOPHRENIA, CHILDHOOD, STRENGTHS, CHILDREN |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Clinical, Edu and Hlth Psychology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10169181 |
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