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Shared genetic etiology between anxiety disorders and psychiatric and related intermediate phenotypes

Published online by Cambridge University Press:  28 March 2019

Kazutaka Ohi Open the ORCID record for Kazutaka Ohi [Opens in a new window] ,
Takeshi Otowa ,
Mihoko Shimada ,
Tsukasa Sasaki  and
Hisashi Tanii
Kazutaka Ohi*
Affiliation:
Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan Department of Neuropsychiatry, Kanazawa Medical University, Ishikawa, Japan
Takeshi Otowa
Affiliation:
Graduate School of Clinical Psychology, Professional Degree Program in Clinical Psychology, Teikyo Heisei University, Tokyo, Japan
Mihoko Shimada
Affiliation:
Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Tsukasa Sasaki
Affiliation:
Department of Physical and Health Education, Graduate School of Education, The University of Tokyo, Tokyo, Japan
Hisashi Tanii
Affiliation:
Center for Physical and Mental Health, Mie University, Mie, Japan Department of Health Promotion and Disease Prevention, Graduate School of Medicine, Mie University, Mie, Japan
*
Author for correspondence: K. Ohi, E-mail: ohi@kanazawa-med.ac.jp
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Abstract

Background

Psychiatric disorders and related intermediate phenotypes are highly heritable and have a complex, overlapping polygenic architecture. A large-scale genome-wide association study (GWAS) of anxiety disorders identified genetic variants that are significant on a genome-wide. The current study investigated the genetic etiological overlaps between anxiety disorders and frequently cooccurring psychiatric disorders and intermediate phenotypes.

Methods

Using case–control and factor score models, we investigated the genetic correlations of anxiety disorders with eight psychiatric disorders and intermediate phenotypes [the volumes of seven subcortical brain regions, childhood cognition, general cognitive ability and personality traits (subjective well-being, loneliness, neuroticism and extraversion)] from large-scale GWASs (n = 7556–298 420) by linkage disequilibrium score regression.

Results

Among psychiatric disorders, the risk of anxiety disorders was positively genetically correlated with the risks of major depressive disorder (MDD) (rg ± standard error = 0.83 ± 0.16, p = 1.97 × 10−7), schizophrenia (SCZ) (0.28 ± 0.09, p = 1.10 × 10−3) and attention-deficit/hyperactivity disorder (ADHD) (0.34 ± 0.13, p = 8.40 × 10−3). Among intermediate phenotypes, significant genetic correlations existed between the risk of anxiety disorders and neuroticism (0.81 ± 0.17, p = 1.30 × 10−6), subjective well-being (−0.73 ± 0.18, p = 4.89 × 10−5), general cognitive ability (−0.23 ± 0.08, p = 4.70 × 10−3) and putamen volume (−0.50 ± 0.18, p = 5.00 × 10−3). No other significant genetic correlations between anxiety disorders and psychiatric or intermediate phenotypes were observed (p > 0.05). The case–control model yielded stronger genetic effect sizes than the factor score model.

Conclusions

Our findings suggest that common genetic variants underlying the risk of anxiety disorders contribute to elevated risks of MDD, SCZ, ADHD and neuroticism and reduced quality of life, putamen volume and cognitive performance. We suggest that the comorbidity of anxiety disorders is partly explained by common genetic variants.

Keywords

Anxiety disordergenetic correlationgenome-wide association studyintermediate phenotypelinkage disequilibrium score regressionmajor depressive disorder
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 4 , March 2020 , pp. 692 - 704
Copyright
Copyright © Cambridge University Press 2019

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