A Mendelian randomization study of the causal association between anxiety phenotypes and schizophrenia.
Anxiety
/ genetics
Anxiety Disorders
/ genetics
Comorbidity
Databases, Genetic
Genetic Association Studies
Genome-Wide Association Study
/ methods
Humans
Mendelian Randomization Analysis
/ methods
Neuroticism
/ physiology
Phenotype
Polymorphism, Single Nucleotide
/ genetics
Random Allocation
Schizophrenia
/ genetics
Mendelian randomization
anxiety
neuroticism
schizophrenia
Journal
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
ISSN: 1552-485X
Titre abrégé: Am J Med Genet B Neuropsychiatr Genet
Pays: United States
ID NLM: 101235742
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
09
12
2019
revised:
19
05
2020
accepted:
28
05
2020
pubmed:
25
6
2020
medline:
15
5
2021
entrez:
25
6
2020
Statut:
ppublish
Résumé
Schizophrenia shows a genetic correlation with both anxiety disorder and neuroticism, a trait strongly associated with anxiety. However, genetic correlations do not discern causality from genetic confounding. We therefore aimed to investigate whether anxiety-related phenotypes lie on the causal pathway to schizophrenia using Mendelian randomization (MR). Four MR methods, each with different assumptions regarding instrument validity, were used to investigate casual associations of anxiety and neuroticism related phenotypes on schizophrenia, and vice versa: inverse variance weighted (IVW), weighted median, weighted mode, and, when appropriate, MR Egger regression. MR provided evidence of a causal effect of neuroticism on schizophrenia (IVW odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.12-1.59), but only weak evidence of a causal effect of anxiety on schizophrenia (IVW OR: 1.10, 95% CI: 1.01-1.19). There was also evidence of a causal association from schizophrenia liability to anxiety disorder (IVW OR: 1.28, 95% CI: 1.18-1.39) and worry (IVW beta: 0.05, 95% CI: 0.03-0.07), but effect estimates from schizophrenia to neuroticism were inconsistent in the main analysis. The evidence of neuroticism increasing schizophrenia risk provided by our results supports future efforts to evaluate neuroticism- or anxiety-based therapies to prevent onset of psychotic disorders.
Identifiants
pubmed: 32578352
doi: 10.1002/ajmg.b.32808
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
360-369Subventions
Organisme : Medical Research Council
ID : MC_UU_00011/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.
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