Abstract P252: Generalization and Fine Mapping of PR Interval Loci in Hispanics: The Population Architecture Using Genomics and Epidemiology (PAGE) Study

摘要: PR interval (PR) prolongation is a predictor of atrial fibrillation, common cardiac arrhythmia, and an established risk factor for pacemaker implantation, heart failure, stroke, all-cause mortality. Previous genome-wide association studies in European (EU) African (AA) descent populations have identified multiple loci associated with PR. However, it unclear whether these are relevant other racial groups, including Hispanic/Latinos (HL). Extending to include admixed such as HL also provides the potential narrow regions identify population specific variants. Therefore, we evaluated 1,135 SNPs from four previously ( SCN5A, SCN10A, CAV1-CAV2, TBX5-TBX3 ), fine-mapped on Illumina Metabochip Associations were examined using linear regression assuming additive genetic model adjusting global ancestry clinical covariates (age, sex, RR interval, body mass index, height, systolic blood pressure) 11,800 participants participating Population Architecture Genomics Epidemiology (PAGE) consortia. Three CAV1-CAV2 ) generalized P 2 >0.2 EU-identified index SNPs). At each loci, stronger evidence than SNP when SCN5A : rs7374540; SCN10A rs6801957; CAV-CAV2 rs717957). Conditional analyses two additional independent at three rs3796387, rs9861242; rs10428132, rs7433723; rs3801995, rs3807994), representing secondary signals. Furthermore, linkage disequilibrium (LD) patterns Hispanics enabled narrowing flanking SNPs. For example, locus, LD indicated that seven rs3807989, SNP, compared 17 rs3807989 applying EU patterns, reducing size region by 71 kilobases. Finally, signals outside which focusing uncorrelated all had based results. In conclusion, same influence important Hispanic populations, although detected These results emphasize importance examining associations diverse order genomic future functional interrogation.