GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals
SCIENTIFIC REPORTS
Authors: Mendez-Giraldez, Raul; Gogarten, Stephanie M.; Below, Jennifer E.; Yao, Jie; Seyerle, Amanda A.; Highland, Heather M.; Kooperberg, Charles; Soliman, Elsayed Z.; Rotter, Jerome I.; Kerr, Kathleen F.; Ryckman, Kelli K.; Taylor, Kent D.; Petty, Lauren E.; Shah, Sanjiv J.; Conomos, Matthew P.; Sotoodehnia, Nona; Cheng, Susan; Heckbert, Susan R.; Sofer, Tamar; Guo, Xiuqing; Whitsel, Eric A.; Lin, Henry J.; Hanis, Craig L.; Laurie, Cathy C.; Avery, Christy L.
Abstract
QT interval prolongation is a heritable risk factor for ventricular arrhythmias and can predispose to sudden death. Most genome-wide association studies (GWAS) of QT were performed in European ancestral populations, leaving other groups uncharacterized. Herein we present the first QT GWAS of Hispanic/Latinos using data on 15,997 participants from four studies. Study-specific summary results of the association between 1000 Genomes Project (1000G) imputed SNPs and electrocardiographically measured QT were combined using fixed-effects meta-analysis. We identified 41 genome-wide significant SNPs that mapped to 13 previously identified QT loci. Conditional analyses distinguished six secondary signals at NOS1AP (n = 2), ATP1B1 (n = 2), SCN5A (n = 1), and KCNQ1 (n = 1). Comparison of linkage disequilibrium patterns between the 13 lead SNPs and six secondary signals with previously reported index SNPs in 1000G super populations suggested that the SCN5A and KCNE1 lead SNPs were potentially novel and population-specific. Finally, of the 42 suggestively associated loci, AJAP1
The Values of Coronary Circulating miRNAs in Patients with Atrial Fibrillation
PLOS ONE
Authors: Xu, Guiyu; Cui, Yuxia; Jia, Zhenghua; Yue, Yunan; Yang, Shuixiang
Abstract
The mechanism of miRNA regulation in atrial fibrillation (AF) occurrence and development is still unclear, especially, the regulating values of coronary circulating miRNAs has not been reported. Based on our AF radiofrequency ablation clinical practice and previous miRNA study, we proposed a hypothesis that the coronary circulating miRNA might much better reflect the regulating state and metabolic level of myocardial miRNA in AF patient. To investigate the regulating values of coronary circulation miRNA, 90 AF patients were selected and compared with 90 healthy subjects, the changes of coronary circulating miRNA differential expression profile in the whole genome were observed in this study. We found out that compared with autologous peripheral blood (PB), 6 miRNAs were upregulated and 8 miRNA downregulated in AF patients' coronary sinus blood (CSB) significantly, especially, the expression of miR-1266, miR-4279 and miR-4666a-3p were obviously increased. Compared with normal donors' peripheral blood, 16 miRNAs were upregulated and 24 miRNAs downregulated dramatically in patients' peripheral blood, among them, the miR-3171 decreased, but miR-892a and miR-3149 increased significantly from the early to end stages of AF. Our results indicated that the coronary circulating miRNA can really reflect the regulating values of miRNA in AF patient; the level of miRNA change in 3 types of AF may reflect the severity of AF clinical and pathophysiological advance; The miR-892a, miR-3171 and miR-3149 may be used as biomarkers for earlier diagnosis, while miR-1266, miR-4279 and miR-4666a-3p may serve as potential intervening targets for AF patient in future.
COA
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