Symptom-level modelling unravels the shared genetic architecture of anxiety and depression

23Andme Research Team

Research output: Contribution to JournalArticleAcademicpeer-review


Depression and anxiety are highly prevalent and comorbid psychiatric traits that cause considerable burden worldwide. Here we use factor analysis and genomic structural equation modelling to investigate the genetic factor structure underlying 28 items assessing depression, anxiety and neuroticism, a closely related personality trait. Symptoms of depression and anxiety loaded on two distinct, although highly genetically correlated factors, and neuroticism items were partitioned between them. We used this factor structure to conduct genome-wide association analyses on latent factors of depressive symptoms (89 independent variants, 61 genomic loci) and anxiety symptoms (102 variants, 73 loci) in the UK Biobank. Of these associated variants, 72% and 78%, respectively, replicated in an independent cohort of approximately 1.9 million individuals with self-reported diagnosis of depression and anxiety. We use these results to characterize shared and trait-specific genetic associations. Our findings provide insight into the genetic architecture of depression and anxiety and comorbidity between them.

Original languageEnglish
Pages (from-to)1432-1442
Number of pages11
JournalNature Human Behaviour
Issue number10
Early online date15 Apr 2021
Publication statusPublished - Oct 2021

Bibliographical note

Funding Information:
We thank the research participants of all cohorts for making this study possible. This work was conducted using the UK Biobank Resource (application number 25331). J.G.T. and A.I.C. are supported by a University of Queensland Research Training Scholarship. N.G.M. received funding from the Australian National Health and Medical Research Council (NHMRC) to conduct surveys in the QIMR Adult Twin Study. S.M. is supported by an NHMRC Fellowship.

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.


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