Single-cell and genome-wide Mendelian randomization identifies causative genes for gout.
Arthritis Res Ther
; 26(1): 114, 2024 Jun 03.
Article
en En
| MEDLINE
| ID: mdl-38831441
ABSTRACT
BACKGROUND:
Gout is a prevalent manifestation of metabolic osteoarthritis induced by elevated blood uric acid levels. The purpose of this study was to investigate the mechanisms of gene expression regulation in gout disease and elucidate its pathogenesis.METHODS:
The study integrated gout genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and methylation quantitative trait loci (mQTL) data for analysis, and utilized two-sample Mendelian randomization study to comprehend the causal relationship between proteins and gout.RESULTS:
We identified 17 association signals for gout at unique genetic loci, including four genes related by protein-protein interaction network (PPI)analysis:
TRIM46, THBS3, MTX1, and KRTCAP2. Additionally, we discerned 22 methylation sites in relation to gout. The study also found that genes such as TRIM46, MAP3K11, KRTCAP2, and TM7SF2 could potentially elevate the risk of gout. Through a Mendelian randomization (MR) analysis, we identified three proteins causally associated with gout ADH1B, BMP1, and HIST1H3A.CONCLUSION:
According to our findings, gout is linked with the expression and function of particular genes and proteins. These genes and proteins have the potential to function as novel diagnostic and therapeutic targets for gout. These discoveries shed new light on the pathological mechanisms of gout and clear the way for future research on this condition.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Predisposición Genética a la Enfermedad
/
Sitios de Carácter Cuantitativo
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Estudio de Asociación del Genoma Completo
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Análisis de la Aleatorización Mendeliana
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Análisis de la Célula Individual
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Gota
Límite:
Humans
Idioma:
En
Revista:
Arthritis Res Ther
Asunto de la revista:
REUMATOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China