Genomics yields biological and phenotypic insights into bipolar disorder

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F25%3A43921486" target="_blank" >RIV/00023752:_____/25:43921486 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41586-024-08468-9" target="_blank" >https://www.nature.com/articles/s41586-024-08468-9</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41586-024-08468-9" target="_blank" >10.1038/s41586-024-08468-9</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Genomics yields biological and phenotypic insights into bipolar disorder

Popis výsledku v původním jazyce

Bipolar disorder is a leading contributor to the global burden of disease(1). Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown(2). We analysed data from participants of European, East Asian, African American and Latino ancestries (n=158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings(3), and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder(4), highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.

Název v anglickém jazyce

Genomics yields biological and phenotypic insights into bipolar disorder

Popis výsledku anglicky

Bipolar disorder is a leading contributor to the global burden of disease(1). Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown(2). We analysed data from participants of European, East Asian, African American and Latino ancestries (n=158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings(3), and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder(4), highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10700 - Other natural sciences

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature

ISSN

0028-0836

e-ISSN

1476-4687

Svazek periodika

639

Číslo periodika v rámci svazku

8056

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

968-975

Kód UT WoS článku

001439581600001

EID výsledku v databázi Scopus

2-s2.0-85217548795