Genetic architectures of cerebral ventricles and their overlap with neuropsychiatric traits

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Yi-Jun Ge - , Zhongshan Hospital at Fudan University (Author)
  • Bang-Sheng Wu - , Zhongshan Hospital at Fudan University (Author)
  • Yi Zhang - , Zhongshan Hospital at Fudan University (Author)
  • Shi-Dong Chen - , Zhongshan Hospital at Fudan University (Author)
  • Ya-Ru Zhang - , Zhongshan Hospital at Fudan University (Author)
  • Ju-Jiao Kang - , Zhongshan Hospital at Fudan University (Author)
  • Yue-Ting Deng - , Zhongshan Hospital at Fudan University (Author)
  • Ya-Nan Ou - , Qingdao University (Author)
  • Xiao-Yu He - , Zhongshan Hospital at Fudan University (Author)
  • Yong-Li Zhao - , Qingdao University (Author)
  • Kevin Kuo - , Zhongshan Hospital at Fudan University (Author)
  • Qing Ma - , Zhongshan Hospital at Fudan University (Author)
  • Tobias Banaschewski - , National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Gareth J Barker - , King's College Hospital NHS Foundation Trust (Author)
  • Arun L W Bokde - , Trinity College Dublin (Author)
  • Sylvane Desrivières - , King's College Hospital NHS Foundation Trust (Author)
  • Herta Flor - , National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Antoine Grigis - , French Alternative Energies and Atomic Energy Commission (CEA) (Author)
  • Hugh Garavan - , Northern Vermont University (Author)
  • Penny Gowland - , Nottingham Trent University (Author)
  • Andreas Heinz - , Charité – Universitätsmedizin Berlin (Author)
  • Rüdiger Brühl - , Physikalisch-Technische Bundesanstalt (Author)
  • Jean-Luc Martinot - , Université Paris-Saclay (Author)
  • Marie-Laure Paillère Martinot - , Université Paris-Saclay (Author)
  • Eric Artiges - , Université Paris-Saclay (Author)
  • Frauke Nees - , National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Dimitri Papadopoulos Orfanos - , French Alternative Energies and Atomic Energy Commission (CEA) (Author)
  • Herve Lemaitre - , French Alternative Energies and Atomic Energy Commission (CEA) (Author)
  • Tomáš Paus - , University of Montreal (Author)
  • Luise Poustka - , University Medical Center Göttingen (Author)
  • Sarah Hohmann - , National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Sabina Millenet - , National Center for Tumor Diseases (NCT) Heidelberg (Author)
  • Juliane H Fröhner - , Department of Psychiatry and Psychotherapy (Author)
  • Michael N Smolka - , Department of Psychiatry and Psychotherapy (Author)
  • Nilakshi Vaidya - , Centre for Population Neuroscience and Precision Medicine (Author)
  • Henrik Walter - , Charité – Universitätsmedizin Berlin (Author)
  • Robert Whelan - , Trinity College Dublin (Author)
  • Jian-Feng Feng - , Zhongshan Hospital at Fudan University, Zhejiang Normal University (Author)
  • Lan Tan - , Qingdao University (Author)
  • Qiang Dong - , Zhongshan Hospital at Fudan University (Author)
  • Gunter Schumann - , Centre for Population Neuroscience and Precision Medicine (Author)
  • Wei Cheng - , Zhongshan Hospital at Fudan University (Author)
  • Jin-Tai Yu - , Zhongshan Hospital at Fudan University (Author)

Abstract

The cerebral ventricles are recognized as windows into brain development and disease, yet their genetic architectures, underlying neural mechanisms and utility in maintaining brain health remain elusive. Here we aggregated genetic and neuroimaging data from 61,974 participants (age range, 9 to 98 years) in five cohorts to elucidate the genetic basis of ventricular morphology and examined their overlap with neuropsychiatric traits. Genome-wide association analysis in a discovery sample of 31,880 individuals identified 62 unique loci and 785 candidate genes associated with ventricular morphology. We replicated over 80% of loci in a well-matched cohort of lateral ventricular volume. Gene set analysis revealed enrichment of ventricular-trait-associated genes in biological processes and disease pathogenesis during both early brain development and degeneration. We explored the age-dependent genetic associations in cohorts of different age groups to investigate the possible roles of ventricular-trait-associated loci in neurodevelopmental and neurodegenerative processes. We describe the genetic overlap between ventricular and neuropsychiatric traits through comprehensive integrative approaches under correlative and causal assumptions. We propose the volume of the inferior lateral ventricles as a heritable endophenotype to predict the risk of Alzheimer's disease, which might be a consequence of prodromal Alzheimer's disease. Our study provides an advance in understanding the genetics of the cerebral ventricles and demonstrates the potential utility of ventricular measurements in tracking brain disorders and maintaining brain health across the lifespan.

Details

Original languageEnglish
JournalNature human behaviour
Publication statusE-pub ahead of print - 19 Oct 2023
Peer-reviewedYes

External IDs

Scopus 85174549596
ORCID /0000-0001-5398-5569/work/150329563
ORCID /0000-0002-8493-6396/work/150330262

Keywords