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Greater genetic risk for adult psychiatric diseases increases vulnerability to adverse outcome after preterm birth

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Original languageEnglish
Article number11443
JournalScientific Reports
Issue number1
Early online date1 Jun 2021
Accepted/In press29 Apr 2021
E-pub ahead of print1 Jun 2021
PublishedDec 2021

Bibliographical note

Funding Information: We gratefully acknowledge the ongoing contribution of the participants in the Twins Early Development Study (TEDS) and their families. TEDS is supported by a program grant to Robert Plomin from the UK Medical Research Council (MR/M021475/1 and previously G0901245). 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 and ERC grant agreement n° 295366. Harriet Cullen is funded by a National Institute for Health Research (NIHR), Academic Clinical Lectureship at King’s College, London for this research project. The work was also supported by the NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Trust, the Wellcome/EPSRC Centre for Medical Engineering at King’s College London and the MRC Centre for Neurodevelopmental Disorders, Kings College London. This paper presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.


King's Authors


Preterm birth is an extreme environmental stress associated with an increased risk of later cognitive dysfunction and mental health problems. However, the extent to which preterm birth is modulated by genetic variation remains largely unclear. Here, we test for an interaction effect between psychiatric polygenic risk and gestational age at birth on cognition at age four. Our sample comprises 4934 unrelated individuals (2066 individuals born < 37 weeks, 918 born < = 34 weeks). Genome-wide polygenic scores (GPS’s) were calculated for each individual for five different psychiatric pathologies: Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder. Linear regression modelling was used to estimate the interaction effect between psychiatric GPS and gestational age at birth (GA) on cognitive outcome for the five psychiatric disorders. We found a significant interaction effect between Schizophrenia GPS and GA (β = 0.038 ± 0.013, p = 6.85 × 10 –3) and Bipolar Disorder GPS and GA (β = 0.038 ± 0.014, p = 6.61 × 10 –3) on cognitive outcome. Individuals with greater genetic risk for Schizophrenia or Bipolar Disorder are more vulnerable to the adverse effects of birth at early gestational age on brain development, as assessed by cognition at age four. Better understanding of gene-environment interactions will inform more effective risk-reducing interventions for this vulnerable population.

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