Family study of bipolar disorder with comorbid anxiety disorder points to THSD7A with possible role of parent‐of‐origin effect

Abstract Aim The aim of this study was to provide new insights into the genetics of bipolar disorder (BD) by analyzing BD comorbid with anxiety disorders. Methods Structured interviews were conducted with BD patients and their parents. Cases were classified into those with comorbid anxiety spectrum...

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Main Authors: Hiroaki Maki, Naomi Sakai, Muneko Kataoka, Kumiko Fujii, Yuki Kageyama, Takashi Hayama, Koji Matsuo, Masaki Nishioka, Tadafumi Kato
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:PCN Reports
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Online Access:https://doi.org/10.1002/pcn5.70071
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author Hiroaki Maki
Naomi Sakai
Muneko Kataoka
Kumiko Fujii
Yuki Kageyama
Takashi Hayama
Koji Matsuo
Masaki Nishioka
Tadafumi Kato
author_facet Hiroaki Maki
Naomi Sakai
Muneko Kataoka
Kumiko Fujii
Yuki Kageyama
Takashi Hayama
Koji Matsuo
Masaki Nishioka
Tadafumi Kato
author_sort Hiroaki Maki
collection DOAJ
description Abstract Aim The aim of this study was to provide new insights into the genetics of bipolar disorder (BD) by analyzing BD comorbid with anxiety disorders. Methods Structured interviews were conducted with BD patients and their parents. Cases were classified into those with comorbid anxiety spectrum (AS) and those without. The family history of patients with BD with comorbid AS was assessed. Focusing on parent‐of‐origin effects and genomic imprinting from the results, imprinted genes and tested single nucleotide polymorphisms (SNPs) in the identified genes were investigated for an association with BD by transmission disequilibrium test (TDT) using published whole‐exome sequencing data. Results The incidence of comorbid AS among all the patients with BD analyzed in this study was 39.6%. Patients with BD whose fathers had AS or mood disorders exhibited a significantly higher rate of AS. Among the known imprinted genes, two were associated with BD: THSD7A and CACNA1C. By pruning SNPs, six variants of the THSD7A exons and four variants of the CACNA1C exons were included in the analysis. Among these, one variant of THSD7A, rs2074603, showed over‐transmission from parents to patients with BD. Furthermore, it was nominally significant only for fathers when TDT was performed separately for fathers and mothers. Conclusion THSD7A may play a role in BD with parent‐of‐origin effects. Further research is necessary to explore the mechanisms by which genomic imprinting is associated with BD. Clinical Trial Registration: N/A.
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spelling doaj-art-a4fbfd9101804543bf7683108ccd23762025-08-20T02:41:45ZengWileyPCN Reports2769-25582025-03-0141n/an/a10.1002/pcn5.70071Family study of bipolar disorder with comorbid anxiety disorder points to THSD7A with possible role of parent‐of‐origin effectHiroaki Maki0Naomi Sakai1Muneko Kataoka2Kumiko Fujii3Yuki Kageyama4Takashi Hayama5Koji Matsuo6Masaki Nishioka7Tadafumi Kato8Department of Psychiatry and Behavioral Science Juntendo University Graduate School of Medicine Tokyo JapanDepartment of Psychiatry and Behavioral Science Juntendo University Graduate School of Medicine Tokyo JapanDepartment of Psychiatry Tokyo Metropolitan Toshima Hospital Tokyo JapanDepartment of Psychiatry Shiga University of Medical Science Otsu JapanDepartment of Neuropsychiatry Graduate School of Medicine, Osaka Metropolitan University Osaka JapanYokohama Mental Clinic Totsuka Yokohama JapanDepartment of Psychiatry Saitama Medical University Moroyama JapanDepartment of Psychiatry and Behavioral Science Juntendo University Graduate School of Medicine Tokyo JapanDepartment of Psychiatry and Behavioral Science Juntendo University Graduate School of Medicine Tokyo JapanAbstract Aim The aim of this study was to provide new insights into the genetics of bipolar disorder (BD) by analyzing BD comorbid with anxiety disorders. Methods Structured interviews were conducted with BD patients and their parents. Cases were classified into those with comorbid anxiety spectrum (AS) and those without. The family history of patients with BD with comorbid AS was assessed. Focusing on parent‐of‐origin effects and genomic imprinting from the results, imprinted genes and tested single nucleotide polymorphisms (SNPs) in the identified genes were investigated for an association with BD by transmission disequilibrium test (TDT) using published whole‐exome sequencing data. Results The incidence of comorbid AS among all the patients with BD analyzed in this study was 39.6%. Patients with BD whose fathers had AS or mood disorders exhibited a significantly higher rate of AS. Among the known imprinted genes, two were associated with BD: THSD7A and CACNA1C. By pruning SNPs, six variants of the THSD7A exons and four variants of the CACNA1C exons were included in the analysis. Among these, one variant of THSD7A, rs2074603, showed over‐transmission from parents to patients with BD. Furthermore, it was nominally significant only for fathers when TDT was performed separately for fathers and mothers. Conclusion THSD7A may play a role in BD with parent‐of‐origin effects. Further research is necessary to explore the mechanisms by which genomic imprinting is associated with BD. Clinical Trial Registration: N/A.https://doi.org/10.1002/pcn5.70071anxiety disordersbipolar disordercomorbiditygenomic imprintingsingle nucleotide polymorphism
spellingShingle Hiroaki Maki
Naomi Sakai
Muneko Kataoka
Kumiko Fujii
Yuki Kageyama
Takashi Hayama
Koji Matsuo
Masaki Nishioka
Tadafumi Kato
Family study of bipolar disorder with comorbid anxiety disorder points to THSD7A with possible role of parent‐of‐origin effect
PCN Reports
anxiety disorders
bipolar disorder
comorbidity
genomic imprinting
single nucleotide polymorphism
title Family study of bipolar disorder with comorbid anxiety disorder points to THSD7A with possible role of parent‐of‐origin effect
title_full Family study of bipolar disorder with comorbid anxiety disorder points to THSD7A with possible role of parent‐of‐origin effect
title_fullStr Family study of bipolar disorder with comorbid anxiety disorder points to THSD7A with possible role of parent‐of‐origin effect
title_full_unstemmed Family study of bipolar disorder with comorbid anxiety disorder points to THSD7A with possible role of parent‐of‐origin effect
title_short Family study of bipolar disorder with comorbid anxiety disorder points to THSD7A with possible role of parent‐of‐origin effect
title_sort family study of bipolar disorder with comorbid anxiety disorder points to thsd7a with possible role of parent of origin effect
topic anxiety disorders
bipolar disorder
comorbidity
genomic imprinting
single nucleotide polymorphism
url https://doi.org/10.1002/pcn5.70071
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