<i>In silico</i> genome‐wide gene‐based association analysis reveals new genes predisposing to coronary artery disease

Zorkoltseva, Irina V.; Shadrina, Alexandra S.; Belonogova, Nadezhda M.; Kirichenko, A. V.; Tsepilov, Yakov A.; Axenovich, Tatiana I.

doi:10.1111/cge.14073

Cited by 3 publications

(2 citation statements)

References 61 publications

(62 reference statements)

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“…6 Recently, we developed a comprehensive, flexible framework for gene-based association analysis that can be applied to summarylevel GWAS results calculated for each variant on biobank-scale sample sizes. 2,36,40 This framework can be incorporated into the analysis of rare and ultrarare (MAF , 0.01%) variants. In addition, the framework includes a polygene pruning procedure aiming to reduce the influence of strong association signals located outside the gene.…”

Section: Introductionmentioning

confidence: 99%

Noncoding rare variants in PANX3 are associated with chronic back pain

Belonogova¹,

Kirichenko²,

Freidin³

et al. 2022

Pain

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Back pain is the leading cause of years lived with disability worldwide, yet surprisingly, little is known regarding the biology underlying this condition. The impact of genetics is known for chronic back pain: its heritability is estimated to be at least 40%. Large genomewide association studies have shown that common variation may account for up to 35% of chronic back pain heritability; rare variants may explain a portion of the heritability not explained by common variants. In this study, we performed the first gene-based association analysis of chronic back pain using UK Biobank imputed data including rare variants with moderate imputation quality. We discovered 2 genes, SOX5 and PANX3, influencing chronic back pain. The SOX5 gene is a well-known back pain gene. The PANX3 gene has not previously been described as having a role in chronic back pain. We showed that the association of PANX3 with chronic back pain is driven by rare noncoding intronic polymorphisms. This result was replicated in an independent sample from UK Biobank and validated using a similar phenotype, dorsalgia, from FinnGen Biobank. We also found that the PANX3 gene is associated with intervertebral disk disorders. We can speculate that a possible mechanism of action of PANX3 on back pain is due to its effect on the intervertebral disks.

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Section: Introductionmentioning

confidence: 99%

Noncoding rare variants in PANX3 are associated with chronic back pain

Belonogova¹,

Kirichenko²,

Freidin³

et al. 2022

Pain

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“…Among those genes, CDK19 was a component of the transcriptional mediator kinase module regulating gene transcription [ 48 ]. Recent studies also found dysregulated CDK19 to be associated with coronary artery diseases [ 49 ]. EGR1 is a key gene in the process of cell differentiation and mitogenesis.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of lncRNA Expression Pattern and Potential Role in Heart Failure Pathology

Chen,

Shi,

Gao

et al. 2023

Disease Markers

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During the last few decades, the morbidity and mortality of heart failure (HF) have remained on an upward trend. Despite the advances in therapeutic and diagnostic measures, there are still many aspects requiring further research. This study is aimed at finding potential long noncoding RNAs (lncRNAs) that could aid with the diagnosis and treatment of HF. We performed RNA sequencing on the peripheral blood of healthy controls as well as HF patients. The expression of lncRNAs was validated by RT-qPCR. Bioinformatic analysis was performed to investigate the possible mechanism of differentially expressed lncRNAs and mRNAs. The diagnostic value of lncRNAs was analysed by ROC analysis. Finally, a total of 207 mRNAs and 422 lncRNAs were identified. GO and KEGG pathway analyses revealed that biological pathways such as immune response, regulation of cell membrane, and transcriptional regulatory process were associated with the pathological progress of HF. The lncRNA-mRNA coexpression network was conducted, and several mRNAs were identified as key potential pathological targets, while lncRNA CHST11, MIR29B2CHG, CR381653.1, and FP236383.2 presented a potential diagnostic value for HF. These findings provide novel insights for the underlying mechanisms and possible therapeutic targets for HF.

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The Role of Furin and Its Therapeutic Potential in Cardiovascular Disease Risk

Fry,

Mazidi,

Kartsonaki

et al. 2024

IJMS

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Furin is an important proteolytic enzyme, converting several proteins from inactive precursors to their active forms. Recently, proteo-genomic analyses in European and East Asian populations suggested a causal association of furin with ischaemic heart disease, and there is growing interest in its role in cardiovascular disease (CVD) aetiology. In this narrative review, we present a critical appraisal of evidence from population studies to assess furin’s role in CVD risk and potential as a drug target for CVD. Whilst most observational studies report positive associations between furin expression and CVD risk, some studies report opposing effects, which may reflect the complex biological roles of furin and its substrates. Genetic variation in FURIN is also associated with CVD and its risk factors. We found no evidence of current clinical development of furin as a drug target for CVD, although several phase 1 and 2 clinical trials of furin inhibitors as a type of cancer immunotherapy have been completed. The growing field of proteo-genomics in large-scale population studies may inform the future development of furin and other potential drug targets to improve the treatment and prevention of CVD.

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In silico genome‐wide gene‐based association analysis reveals new genes predisposing to coronary artery disease

Cited by 3 publications

References 61 publications

Noncoding rare variants in PANX3 are associated with chronic back pain

Noncoding rare variants in PANX3 are associated with chronic back pain

Evaluation of lncRNA Expression Pattern and Potential Role in Heart Failure Pathology

The Role of Furin and Its Therapeutic Potential in Cardiovascular Disease Risk

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