Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression

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  • Joanna Martin, Cardiff University
  • ,
  • Kimiya Asjadi, Cardiff University
  • ,
  • Leon Hubbard, Cardiff University
  • ,
  • Kimberley Kendall, Cardiff University
  • ,
  • Antonio F. Pardiñas, Cardiff University
  • ,
  • Bradley Jermy, King's College London
  • ,
  • Cathryn M. Lewis, King's College London
  • ,
  • Bernhard T. Baune, University of Münster, Melbourne Medical School, University of Melbourne
  • ,
  • Dorret I. Boomsma, Vrije Universiteit Amsterdam
  • ,
  • Steven P. Hamilton, Kaiser Permanente
  • ,
  • Susanne Lucae, Max Planck Institute of Psychiatry
  • ,
  • Patrik K. Magnusson, Karolinska Institutet
  • ,
  • Nicholas G. Martin, Queensland Institute of Medical Research
  • ,
  • Andrew M. McIntosh, University of Edinburgh
  • ,
  • Divya Mehta, Queensland University of Technology
  • ,
  • Ole Mors
  • Niamh Mullins, King's College London, Icahn School of Medicine at Mount Sinai
  • ,
  • Brenda W.J.H. Penninx, Vrije Universiteit Amsterdam
  • ,
  • Martin Preisig, University of Lausanne
  • ,
  • Marcella Rietschel, Heidelberg University 
  • ,
  • Ian Jones, Cardiff University
  • ,
  • James T.R. Walters, Cardiff University
  • ,
  • Frances Rice, Cardiff University
  • ,
  • Anita Thapar, Cardiff University
  • ,
  • Michael O'Donovan, Cardiff University

Anxiety and depression are common mental health disorders and have a higher prevalence in females. They are modestly heritable, share genetic liability with other psychiatric disorders, and are highly heterogeneous. There is evidence that genetic liability to neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) is associated with anxiety and depression, particularly in females. We investigated sex differences in family history for neurodevelopmental and psychiatric disorders and neurodevelopmental genetic risk burden (indexed by ADHD polygenic risk scores (PRS) and rare copy number variants; CNVs) in individuals with anxiety and depression, also taking into account age at onset. We used two complementary datasets: 1) participants with a self-reported diagnosis of anxiety or depression (N = 4,178, 65.5% female; mean age = 41.5 years; N = 1,315 with genetic data) from the National Centre for Mental Health (NCMH) cohort and 2) a clinical sample of 13,273 (67.6% female; mean age = 45.2 years) patients with major depressive disorder (MDD) from the Psychiatric Genomics Consortium (PGC). We tested for sex differences in family history of psychiatric problems and presence of rare CNVs (neurodevelopmental and >500kb loci) in NCMH only and for sex differences in ADHD PRS in both datasets. In the NCMH cohort, females were more likely to report family history of neurodevelopmental and psychiatric disorders, but there were no robust sex differences in ADHD PRS or presence of rare CNVs. There was weak evidence of higher ADHD PRS in females compared to males in the PGC MDD sample, particularly in those with an early onset of MDD. These results do not provide strong evidence of sex differences in neurodevelopmental genetic risk burden in adults with anxiety and depression. This indicates that sex may not be a major index of neurodevelopmental genetic heterogeneity, that is captured by ADHD PRS and rare CNV burden, in adults with anxiety and depression.

Original languageEnglish
Article numbere0248254
JournalPLOS ONE
Volume16
Issue9
ISSN1932-6203
DOIs
Publication statusPublished - Sep 2021

Bibliographical note

Publisher Copyright:
© 2021 Martin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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