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Immune signatures and disorder-specific patterns in a cross-disorder gene expression analysis

  • Simone de Jong (a1), Stephen J. Newhouse (a1), Hamel Patel (a1), Sanghyuck Lee (a1), David Dempster (a1), Charles Curtis (a1), Jose Paya-Cano (a1), Declan Murphy (a2), C. Ellie Wilson (a3), Jamie Horder (a4), M. Andreina Mendez (a4), Philip Asherson (a5), Margarita Rivera (a6), Helen Costello (a7), Stefanos Maltezos (a8), Susannah Whitwell (a8), Mark Pitts (a8), Charlotte Tye (a9), Karen L. Ashwood (a10), Patrick Bolton (a9), Sarah Curran (a11), Peter McGuffin (a5), Richard Dobson (a1) and Gerome Breen (a1)...

Abstract

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.

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Copyright

Corresponding author

Gerome Breen, MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, UK. Email: gerome.breen@gmail.com

Footnotes

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Declaration of interest

G.B. acts a consultant in preclinical genomics for Eli Lilly.

Footnotes

References

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Immune signatures and disorder-specific patterns in a cross-disorder gene expression analysis

  • Simone de Jong (a1), Stephen J. Newhouse (a1), Hamel Patel (a1), Sanghyuck Lee (a1), David Dempster (a1), Charles Curtis (a1), Jose Paya-Cano (a1), Declan Murphy (a2), C. Ellie Wilson (a3), Jamie Horder (a4), M. Andreina Mendez (a4), Philip Asherson (a5), Margarita Rivera (a6), Helen Costello (a7), Stefanos Maltezos (a8), Susannah Whitwell (a8), Mark Pitts (a8), Charlotte Tye (a9), Karen L. Ashwood (a10), Patrick Bolton (a9), Sarah Curran (a11), Peter McGuffin (a5), Richard Dobson (a1) and Gerome Breen (a1)...
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