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.
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All GWAS summary statistics generated from UK Biobank data are available from the authors upon request. Individual-level data for UK Biobank participants are available to eligible researchers through the UK Biobank (www.biobank.ac.uk). Access to 23andMe data is available upon request to 23andMe (further information is available from https://research.23andme.com/collaborate/).
Code used to conduct analyses presented in this manuscript is available from the authors upon reasonable request.
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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.
W.W., S.S. and members of the 23andMe Research Team are employees of 23andMe Inc. The other authors declare no competing interests.
Peer review information Nature Human Behaviour thanks Evangelos Evangelou and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Thorp, J.G., Campos, A.I., Grotzinger, A.D. et al. Symptom-level modelling unravels the shared genetic architecture of anxiety and depression. Nat Hum Behav 5, 1432–1442 (2021). https://doi.org/10.1038/s41562-021-01094-9
Nature Reviews Methods Primers (2021)