Genome-Wide Association and Functional Studies Identify
            <i>SCML4</i>
            and
            <i>THSD7A</i>
            as Novel Susceptibility Genes for Coronary Artery Disease

Li, Yang; Wang, Dao Wen; Chen, Yundai; Chen, Can; Guo, Jian; Zhang, Shu; Sun, Zhijun; Ding, Hu; Yao, Yan; Zhou, Lei; Xu, Ke; Song, Chun; Yang, Fan; Zhao, Bi; Yan, Han; Wang, Wenjing; Wu, Chong; Lu, Xiangfeng; Yang, Xueli; Dong, Jie; Zheng, Gu-Yan; Tian, Senlin; Cui, Yanjun; Li-juan, Jin; Liu, Gangqiong; Cui, Hanbin; Wang, Sheng-Huang; Jiang, Feng; Wang, Changhua; Erdmann, Jeanette; Zeng, Linyao; Huang, Shian; Zhong, Jianfeng; Ma, Yuanyuan; Chen, Wenjiang; Sun, Junhao; Wei, Lei; Chen, Shenghan; Rao, Shaoqi; Gu, Dongfeng; Schunkert, Heribert; Tian, Xiao-Li

doi:10.1161/atvbaha.117.310594

Cited by 42 publications

(26 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…TBX5 is potentially regulated by miR-4455 and it is considered as a key regulator of heart development [56]. Similarly, it was indicated that Scm Polycomb Group Protein Like 4, encoded by SCML4, participates in atherosclerosis mechanism that can lead to ischemic heart disease [57]. In our study, IPA analysis has shown, that miR-1224-5p is involved in the regulation of SCML4 gene.…”

Section: Discussionsupporting

confidence: 60%

Serum miRNA Profile in Diabetic Patients with Ischemic Heart Disease as a Promising non-invasive Biomarker

Bielska¹,

Bauer²,

Szałkowska³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background The increasing morbidity and mortality of type 2 diabetic mellitus (T2DM) patients with ischemic heart disease (IHD) highlights an urgent need to identify early biomarkers, which would help to predict individual risk of development of IHD. Here, we postulate that circulating serum-derived miRNAs may serve as potential biomarkers for early IHD diagnosis and help to identify diabetic individuals with a predisposition to undergo IHD. Methods We obtained serum samples from T2DM patients either with IHD or IHD-free and analysed the expression levels of 798 miRNAs using the NanoString nCounter Technology Platform. The prediction of the putative miRNAs targets was performed using the Ingenuity Pathway Analysis (IPA) software. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of identified miRNAs. Results Our data showed that 9 miRNAs (miR-1224-5p, miR-1303, miR-3147, miR-4455, miR-498, miR-548b-3p, miR-548d-3p, miR-615-3p, miR-651-5p) were significantly upregulated in T2DM IHD patients compared to T2DM patients without IHD. In patients with upregulated miRNA, functional enrichment analysis of target genes by IPA indicated networks and canonical pathways involved in the pathology of the cardiovascular system. All tested miRNAs showed high diagnostic value (AUC > 0.8). Conclusions Taken together, our findings suggest that circulating miRNAs might have a crucial role in the development of IHD in diabetic patients and may be used as a potential biomarker for early diagnosis.

show abstract

Section: Discussionsupporting

confidence: 60%

Serum miRNA Profile in Diabetic Patients with Ischemic Heart Disease as a Promising non-invasive Biomarker

Bielska¹,

Bauer²,

Szałkowska³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Especially, We focus on the co-expression relationship pairs associated with lncRNA ENST00000607042 to explore the potential biological functions in IA. We found that SCML4 is associated with endothelial dysfunction and vascular remodeling [21]. CXCR4, another mRNA co-expressed with lncRNA ENST00000607042, has been reported to be likely to regulate chemotaxis and adhesion through the CXCR4-SDF-1 pathway, which is closely related to cardiac and macrovascular development [45].…”

Section: Discussionmentioning

confidence: 86%

“…Interestingly, we observed many mRNAs that may be involved in the pathogenesis of IA. Such as Eukaryotic elongation factor 2 kinase (EEF2K) [ 20 ], Scm polycomb group protein-like 4 (SCML4) [ 21 ], Matrix metalloproteinases 19 (MMP19) [ 22 ], Lymphoid enhancer factor 1 (LEF1) [ 23 ]. The further GO analyses revealed that the co-expression genes of the 5 candidate lncRNAs were related to T cell activation and leukocyte activation, etc.…”

Section: Resultsmentioning

confidence: 99%

Exploring the association of long noncoding RNA expression profiles with intracranial aneurysms, based on sequencing and related bioinformatics analysis

et al. 2020

View full text Add to dashboard Cite

Background The present study aims to investigate the complete long non-coding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in Intracranial aneurysm (IA) patients and controls by RNA sequencing, which reveals the lncRNA with predictive value for IA risk. Methods The comprehensive lncRNA and mRNA expression profiles were detected by RNA-Seq in human IA walls and superficial temporal arteries (STAs), followed by bioinformatics analyses, such as GO analysis, KEGG pathway analysis, and CNC network construction. Subsequently, qRT-PCR was used to profile the expression levels of selected lncRNA (lncRNA ENST000000576153, lncRNA ENST00000607042, lncRNA ENST00000471220, lncRNA ENST00000478738, lncRNA MALAT1, lncRNA ENST00000508090 and lncRNA ENST00000579688) in 30 (small) or 130 (large) peripheral blood leukocytes, respectively. Multivariate logistic regression was utilized to analyze the effects of lncRNA on IA. Receiver operating characteristic (ROC) curve was further drawn to explore the value of lncRNA in predicting IA. Results Totally 900 up-regulated and 293 down-regulated lncRNAs, as well as 1297 up-regulated and 831 down-regulated mRNAs were discovered in sequencing. Enrichment analyses revealed that they were actively involved in immune/inflammatory response and cell adhesion/extracellular matrix. Co-expression analysis and further enrichment analyses showed that five candidate lncRNAs might participate in IA’s inflammatory response. Besides, after controlling other conventional risk factors, multivariate logistic regression analysis disclosed that low expression of lncRNA ENST00000607042, lncRNA ENST00000471220, lncRNA ENST00000478738, lncRNA MALAT1 in peripheral blood leukocytes were independent risk factors for IA. LncRNA ENST00000607042 has superior diagnostic value for IA. Conclusions This study reveals the complete lncRNAs expression profiles in IA. The inflammatory response was closely related to IA. Besides, lncRNA ENST00000607042 might be a novel biomarker for IA risk.

show abstract

“…We further investigated the genetic association with specific lung cancer histological subtypes and identified additional 22 novel loci achieving genome-wide significance (Table 2 and Supplementary Table 2 We observed a novel association in Thrombospondin type 1 domain containing 7A (THSD7A) at rs111754768 on 7p21.3 that demonstrated a strong genetic signal in African-ancestry subjects. THSD7A is known for coronary artery disease susceptibility 49 . We found novel SNPs with strong evidence of associations with SCC at rs139904273 in DLC1 on 8p22 and at rs182805930 in VPS13B on 8q22.2 presenting significant genetic signal in African-ancestry populations, and intergenic variant rs192523071 near CSMD3 on 8q23.3 with significant signal in European-ancestry populations.…”

Section: Resultsmentioning

confidence: 99%

Trans-ethnic genome-wide meta-analysis of 35,732 cases and 34,424 controls identifies novel genomic cross-ancestry loci contributing to lung cancer susceptibility

Byun

Han

et al. 2020

Preprint

View full text Add to dashboard Cite

Lung cancer is the leading cause of cancer death worldwide. Genome-wide association studies have revealed genetic risk factors, highlighting the role of smoking, family history, telomere regulation, and DNA damage-repair in lung cancer etiology. Many studies have focused on a single ethnic group to avoid confounding from variability in allele frequencies across populations; however, comprehensive multi-ethnic analyses may identify variants that are more likely to be causal. This large-scale, multi-ethnic meta-analyses identified 28 novel risk loci achieving genome-wide significance. Leading candidates were further studied using single-cell methods for evaluating DNA-damage. DNA-damage promoting activities were confirmed for selected genes by knockdown genes and overexpression studies.

show abstract

Genome-Wide Association and Functional Studies Identify SCML4 and THSD7A as Novel Susceptibility Genes for Coronary Artery Disease

Abstract: We identify 3 novel loci associated with CAD and show that 2 genes, and, make functional contributions to atherosclerosis. How rs852787 and its host gene are linked to CAD needs further studies.

Cited by 42 publications

References 47 publications

Serum miRNA Profile in Diabetic Patients with Ischemic Heart Disease as a Promising non-invasive Biomarker

Serum miRNA Profile in Diabetic Patients with Ischemic Heart Disease as a Promising non-invasive Biomarker

Exploring the association of long noncoding RNA expression profiles with intracranial aneurysms, based on sequencing and related bioinformatics analysis

Trans-ethnic genome-wide meta-analysis of 35,732 cases and 34,424 controls identifies novel genomic cross-ancestry loci contributing to lung cancer susceptibility

Contact Info

Product

Resources

About