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.
| Original language | English |
|---|---|
| Pages (from-to) | 1588-1598 |
| Number of pages | 11 |
| Journal | Molecular Psychiatry |
| Volume | 27 |
| Issue number | 3 |
| Early online date | 28 Feb 2022 |
| DOIs | |
| Publication status | E-pub ahead of print - 28 Feb 2022 |
Bibliographical note
Funding Information:We are extremely grateful to all the ALSPAC families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and FS and BSTP will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ). ALSPAC GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. The authors gratefully acknowledge the ongoing contribution of the participants in the TEDS and their families. TEDS is supported by a programme grant to RP from the UK Medical Research Council (MR/M021475/1 and previously G0901245), with additional support from the US National Institutes of Health (AG046938). BSTP and SEF are supported by the Max Planck Society. BSTP is supported by the Simons Foundation (Award ID: 514787). The authors also thank Oliver Pain and Wolfgang Viechtbauer for helpful discussions. RP is supported by a Medical Research Council Professorship award (G19/2). The research leading to these results has also received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ grant agreement n° 602768. This project has received funding from the European Union’s Horizon 2020 research and innovation programme, Marie Sklodowska Curie Actions (MSCA-ITN-2016) Innovative Training Networks (CAPICE grant 721567). KR is supported by a Sir Henry Wellcome Postdoctoral Fellowship.
Funding Information:
We are extremely grateful to all the ALSPAC families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and FS and BSTP will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). ALSPAC GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. The authors gratefully acknowledge the ongoing contribution of the participants in the TEDS and their families. TEDS is supported by a programme grant to RP from the UK Medical Research Council (MR/M021475/1 and previously G0901245), with additional support from the US National Institutes of Health (AG046938). BSTP and SEF are supported by the Max Planck Society. BSTP is supported by the Simons Foundation (Award ID: 514787). The authors also thank Oliver Pain and Wolfgang Viechtbauer for helpful discussions. RP is supported by a Medical Research Council Professorship award (G19/2). The research leading to these results has also received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ grant agreement n° 602768. This project has received funding from the European Union’s Horizon 2020 research and innovation programme, Marie Sklodowska Curie Actions (MSCA-ITN-2016) Innovative Training Networks (CAPICE grant 721567). KR is supported by a Sir Henry Wellcome Postdoctoral Fellowship.
Publisher Copyright:
© 2022, The Author(s).
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