Symptom-level Modelling Unravels the Shared Genetic Architecture of Anxiety and Depression

Overview

Journal Nat Hum Behav

Specialties Psychology
Social Sciences

Date 2021 Apr 16

PMID 33859377

Citations 41

Authors

Jackson G Thorp

Adrian I Campos

Andrew D Grotzinger

Zachary F Gerring

Jiyuan An

Jue-Sheng Ong

Wei Wang

Suyash Shringarpure

Enda M Byrne

Stuart Macgregor

Nicholas G Martin

Sarah E Medland

Christel M Middeldorp

Eske M Derks

Affiliations

Soon will be listed here.

Abstract

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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