Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital

Association of Whole-Genome and NETRIN1 Signaling Pathway–Derived Polygenic Risk Scores for Major Depressive Disorder and White Matter Microstructure in the UK Biobank

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Bereavement Among Adult Siblings: An Examination of Health Services Utilization and Mental Health Outcomes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Miruna C. Barbu
  • Yanni Zeng
  • Xueyi Shen
  • Simon R. Cox
  • Toni Kim Clarke
  • Jude Gibson
  • Mark J. Adams
  • Mandy Johnstone
  • Chris S. Haley
  • Stephen M. Lawrie
  • Ian J. Deary
  • Naomi R. Wray
  • Stephan Ripke
  • Manuel Mattheisen
  • Maciej Trzaskowski
  • Enda M. Byrne
  • Abdel Abdellaoui
  • Mark J. Adams
  • Esben Agerbo
  • Tracy M. Air
  • Till F.M. Andlauer
  • Silviu Alin Bacanu
  • Marie Bækvad-Hansen
  • Aartjan T.F. Beekman
  • Tim B. Bigdeli
  • Elisabeth B. Binder
  • Douglas H.R. Blackwood
  • Julien Bryois
  • Henriette N. Buttenschøn
  • Jonas Bybjerg-Grauholm
  • Na Cai
  • Enrique Castelao
  • Jane Hvarregaard Christensen
  • Toni Kim Clarke
  • Jonathan R.I. Coleman
  • Lucía Colodro-Conde
  • Baptiste Couvy-Duchesne
  • Nick Craddock
  • Gregory E. Crawford
  • Gail Davies
  • Ian J. Deary
  • Franziska Degenhardt
  • Eske M. Derks
  • Nese Direk
  • Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
  • Thomas F. Hansen (Member of study group)
  • Jesper Krogh (Member of study group)
  • Wesley Thompson (Member of study group)
  • Shantel Marie Weinsheimer (Member of study group)
  • Merete Nordentoft (Member of study group)
  • Thomas Werge (Member of study group)
  • 23andMe Research Team
View graph of relations

Background: Major depressive disorder is a clinically heterogeneous psychiatric disorder with a polygenic architecture. Genome-wide association studies have identified a number of risk-associated variants across the genome and have reported growing evidence of NETRIN1 pathway involvement. Stratifying disease risk by genetic variation within the NETRIN1 pathway may provide important routes for identification of disease mechanisms by focusing on a specific process, excluding heterogeneous risk-associated variation in other pathways. Here, we sought to investigate whether major depressive disorder polygenic risk scores derived from the NETRIN1 signaling pathway (NETRIN1-PRSs) and the whole genome, excluding NETRIN1 pathway genes (genomic-PRSs), were associated with white matter microstructure. Methods: We used two diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), in the most up-to-date UK Biobank neuroimaging data release (FA: n = 6401; MD: n = 6390). Results: We found significantly lower FA in the superior longitudinal fasciculus (β = −.035, pcorrected =.029) and significantly higher MD in a global measure of thalamic radiations (β =.029, pcorrected =.021), as well as higher MD in the superior (β =.034, pcorrected =.039) and inferior (β =.029, pcorrected =.043) longitudinal fasciculus and in the anterior (β =.025, pcorrected =.046) and superior (β =.027, pcorrected =.043) thalamic radiation associated with NETRIN1-PRS. Genomic-PRS was also associated with lower FA and higher MD in several tracts. Conclusions: Our findings indicate that variation in the NETRIN1 signaling pathway may confer risk for major depressive disorder through effects on a number of white matter tracts.

Original languageEnglish
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Issue number1
Pages (from-to)91-100
Publication statusPublished - 2019

Bibliographical note

Copyright © 2018 Society of Biological Psychiatry. All rights reserved.

    Research areas

  • Biological pathway, Major depressive disorder, NETRIN1, Polygenic risk score, Thalamic radiations, White matter

ID: 55294980