Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F22%3A43920996" target="_blank" >RIV/00023752:_____/22:43920996 - isvavai.cz</a>

Alternative codes found

RIV/00064203:_____/22:10437768 RIV/00216208:11130/22:10437768

Result on the web

<a href="https://reader.elsevier.com/reader/sd/pii/S0006322321011392?token=BE78B08B824821DEAA34473D05446925346A8B38B180C4A11C277EC41EE044F0CC0D9F5E4D43A4D412C1E53790E512C0&originRegion=eu-west-1&originCreation=20230108205420" target="_blank" >https://reader.elsevier.com/reader/sd/pii/S0006322321011392?token=BE78B08B824821DEAA34473D05446925346A8B38B180C4A11C277EC41EE044F0CC0D9F5E4D43A4D412C1E53790E512C0&originRegion=eu-west-1&originCreation=20230108205420</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.biopsych.2021.02.972" target="_blank" >10.1016/j.biopsych.2021.02.972</a>

Result language

angličtina

Original language name

Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Original language description

Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p &lt; 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p &lt; .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30215 - Psychiatry

Project

—

Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2022

Confidentiality

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

Name of the periodical

Biological Psychiatry

ISSN

0006-3223

e-ISSN

1873-2402

Volume of the periodical

91

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

16

Pages from-to

102-117

UT code for WoS article

000747756000015

EID of the result in the Scopus database

2-s2.0-85108284544