Identification of candidate genes associated with bipolar disorder by whole-exome sequencing of a Chinese multi-affected pedigree

Abstract Background Bipolar disorder (BD) is a severe mental disorder with high, approximately 70% heritability. Here, to identify novel risk genes of BD, we conducted whole-exome sequencing and pathway enrichment analyses across one multi-affected, southern Chinese Han pedigree. Methods Whole-exome...

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Bibliographic Details
Main Authors: Yiyang Wang, Zhen Xu, Yinnan Zhang, Hui Li
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Psychiatry
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Online Access:https://doi.org/10.1186/s12888-025-07002-z
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Summary:Abstract Background Bipolar disorder (BD) is a severe mental disorder with high, approximately 70% heritability. Here, to identify novel risk genes of BD, we conducted whole-exome sequencing and pathway enrichment analyses across one multi-affected, southern Chinese Han pedigree. Methods Whole-exome sequencing (WES) was performed on five patients with BD and three unaffected members in one multi-affected pedigree. The analyses focused on variants that (i) were shared by affected members but were not present in the unaffected members, and (ii) were rare and damaging. Bioinformatic analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, were used for functional annotation and pathway analysis. Results We identified a rare and potentially damaging single nucleotide variations (SNVs) in NTN1, MYH10, and RILP that were shared by affected family members but were absent in unaffected members. Their functions were predicted to be associated with actin binding, substrate-dependent cell migration, actin cytoskeleton, and nucleotide excision repair. Conclusion Our findings suggest that NTN1, MYH10, and RILP may represent novel candidate risk genes for BD, although further validation in larger cohorts is needed.
ISSN:1471-244X