A Genetic Polymorphism in the WDR72 Gene is Associated With Calcium Nephrolithiasis in the Chinese Han Population

Wang, Lujia; Zhou, Zijian; Yang, Yuanyuan; Gao, Peng; Lin, Xiaoling; Wu, Zhong

doi:10.3389/fgene.2022.897051

Cited by 3 publications

(1 citation statement)

References 38 publications

(53 reference statements)

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“…DOCK7 is associated with serum lipid level ( 39 ), which are known to play a role in both sepsis and kidney health ( 40 ). Finally, HIBADH , previously connected to kidney stones ( 41 ), has been documented to be involved in valine metabolism disorders ( 42 ),a pathway recently implicated in sepsis ( 43 ). The established roles of these genes in inflammation, lipid metabolism, and metabolic disorders, alongside our findings in sepsis and kidney diseases, suggest a potential interplay in the pathogenesis of these conditions.…”

Section: Discussionmentioning

confidence: 99%

Shared genetic correlations between kidney diseases and sepsis

Zhang,

Cui,

Jiang

et al. 2024

Front. Endocrinol.

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BackgroundClinical studies have indicated a comorbidity between sepsis and kidney diseases. Individuals with specific mutations that predispose them to kidney conditions are also at an elevated risk for developing sepsis, and vice versa. This suggests a potential shared genetic etiology that has not been fully elucidated.MethodsSummary statistics data on exposure and outcomes were obtained from genome-wide association meta-analysis studies. We utilized these data to assess genetic correlations, employing a pleiotropy analysis method under the composite null hypothesis to identify pleiotropic loci. After mapping the loci to their corresponding genes, we conducted pathway analysis using Generalized Gene-Set Analysis of GWAS Data (MAGMA). Additionally, we utilized MAGMA gene-test and eQTL information (whole blood tissue) for further determination of gene involvement. Further investigation involved stratified LD score regression, using diverse immune cell data, to study the enrichment of SNP heritability in kidney-related diseases and sepsis. Furthermore, we employed Mendelian Randomization (MR) analysis to investigate the causality between kidney diseases and sepsis.ResultsIn our genetic correlation analysis, we identified significant correlations among BUN, creatinine, UACR, serum urate, kidney stones, and sepsis. The PLACO analysis method identified 24 pleiotropic loci, pinpointing a total of 28 nearby genes. MAGMA gene-set enrichment analysis revealed a total of 50 pathways, and tissue-specific analysis indicated significant enrichment of five pairs of pleiotropic results in kidney tissue. MAGMA gene test and eQTL information (whole blood tissue) identified 33 and 76 pleiotropic genes, respectively. Notably, genes PPP2R3A for BUN, VAMP8 for UACR, DOCK7 for creatinine, and HIBADH for kidney stones were identified as shared risk genes by all three methods. In a series of immune cell-type-specific enrichment analyses of pleiotropy, we identified a total of 37 immune cells. However, MR analysis did not reveal any causal relationships among them.ConclusionsThis study lays the groundwork for shared etiological factors between kidney and sepsis. The confirmed pleiotropic loci, shared pathogenic genes, and enriched pathways and immune cells have enhanced our understanding of the multifaceted relationships among these diseases. This provides insights for early disease intervention and effective treatment, paving the way for further research in this field.

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