Shared genetic basis and causality between schizophrenia and inflammatory bowel disease: evidence from a comprehensive genetic analysis.
Psychol Med
; 54(10): 2658-2668, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38563283
ABSTRACT
BACKGROUND:
The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear.METHODS:
By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders.RESULTS:
SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.071.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.061.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.041.18, p = 1.84 × 10−3).CONCLUSIONS:
We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
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Doenças Inflamatórias Intestinais
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Predisposição Genética para Doença
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Estudo de Associação Genômica Ampla
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Análise da Randomização Mendeliana
Limite:
Humans
Idioma:
En
Revista:
Psychol Med
/
Psychol. med
/
Psychological medicine
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China