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Immune signatures and disorder-specific patterns in a cross-disorder gene expression analysis
Simone de Jong1, Stephen J Newhouse1, Hamel Patel1
1Simone de Jong, PhD, Stephen J. Newhouse, PhD, Hamel Patel, Sanghyuck Lee, David Dempster, Charles Curtis, MSc, Jose Paya-Cano, PhD, MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London and NIHR Biomedical Research Centre for Mental Health, Maudsley Hospital and Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Declan Murphy, MD, The Sackler Institute for Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; C. Ellie Wilson, PhD, The Sackler Institute for Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London UK and Individual Differences, Language and Cognition Lab, Department of Developmental and Educational Psychology, University of Seville, Spain; Jamie Horder, PhD, M. Andreina Mendez, PhD, The Sackler Institute for Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London; Philip Asherson, PhD, MD, MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Margarita Rivera, PhD, MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK and CIBERSAM-University of Granada and Instituto de Investigación Biosanitaria ibs. GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain; Helen Costello, PhD, Wolfson Centre for Age Related Diseases, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK; Stefanos Maltezos, MSc, MD, Susannah Whitwell, MD, Mark Pitts, Adult ADHD Service, South London and Maudsley NHS Foundation Trust, London, UK; Charlotte T
Background:
Recent studies point to overlap between neuropsychiatric disorders in symptomatology and genetic aetiology.
Aims:
To systematically investigate genomics overlap between childhood and adult attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and major depressive disorder (MDD).
Method:
Analysis of whole-genome blood gene expression and genetic risk scores of 318 individuals. Participants included individuals affected with adult ADHD (n = 93), childhood ADHD (n = 17), MDD (n = 63), ASD (n = 51), childhood dual diagnosis of ADHD-ASD (n = 16) and healthy controls (n = 78).
Results:
Weighted gene co-expression analysis results reveal disorder-specific signatures for childhood ADHD and MDD, and also highlight two immune-related gene co-expression modules correlating inversely with MDD and adult ADHD disease status. We find no significant relationship between polygenic risk scores and gene expression signatures.
Conclusions:
Our results reveal disorder overlap and specificity at the genetic and gene expression level. They suggest new pathways contributing to distinct pathophysiology in psychiatric disorders and shed light on potential shared genomic risk factors.
