Fine-mapping genomic loci refines bipolar disorder risk genes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F24%3A43921586" target="_blank" >RIV/00023752:_____/24:43921586 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1038/s41593-025-01998-z" target="_blank" >https://doi.org/10.1038/s41593-025-01998-z</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41593-025-01998-z" target="_blank" >10.1038/s41593-025-01998-z</a>
Alternative languages
Result language
angličtina
Original language name
Fine-mapping genomic loci refines bipolar disorder risk genes
Original language description
Bipolar disorder is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 bipolar disorder risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci and prioritized 17 likely causal SNPs for bipolar disorder. We mapped these SNPs to genes and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci and results from rare variant exome sequencing in bipolar disorder. Convergent lines of evidence supported the roles of genes involved in neurotransmission and neurodevelopment, including SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, FKBP2, RASGRP1, FURIN, FES, MED24 and THRA among others in bipolar disorder. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance of bipolar disorder polygenic risk scores across diverse populations and present a high-throughput fine-mapping pipeline.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
—
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Neuroscience
ISSN
1097-6256
e-ISSN
1546-1726
Volume of the periodical
28
Issue of the periodical within the volume
7
Country of publishing house
DE - GERMANY
Number of pages
11
Pages from-to
1393-1403
UT code for WoS article
001516388000001
EID of the result in the Scopus database
2-s2.0-105008875276