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

Identifikátory výsledku

  • Kód výsledku v 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>

  • Nalezeny alternativní kódy

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

  • Výsledek na webu

    <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>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

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

  • Popis výsledku v původním jazyce

    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.

  • Název v anglickém jazyce

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

  • Popis výsledku anglicky

    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.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    30215 - Psychiatry

Návaznosti výsledku

  • Projekt

  • Návaznosti

    V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Ostatní

  • Rok uplatnění

    2022

  • Kód důvěrnosti údajů

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

Údaje specifické pro druh výsledku

  • Název periodika

    Biological Psychiatry

  • ISSN

    0006-3223

  • e-ISSN

    1873-2402

  • Svazek periodika

    91

  • Číslo periodika v rámci svazku

    1

  • Stát vydavatele periodika

    US - Spojené státy americké

  • Počet stran výsledku

    16

  • Strana od-do

    102-117

  • Kód UT WoS článku

    000747756000015

  • EID výsledku v databázi Scopus

    2-s2.0-85108284544