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Background  Genome-wide association studies (GWAS) identified multiple loci for blood pressure (BP) and hypertension. Six genes –  ATP2B1 ,  CACNB2 ,  CYP17A1 ,  JAG1 ,  PLEKHA7 , and  SH2B3  – were evaluated for sequence variation with large effects on systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP).    Methods and Results  Targeted genomic sequence was determined in 4,178 European ancestry participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Common variants (≥50 minor allele copies) were evaluated individually and rare variants (minor allele frequency, MAF≤1%) were aggregated by locus. 464 common variants were identified across the 6 genes. An upstream  CYP17A1  variant, rs11191416 (MAF = 0.09), was the most significant association for SBP (P = 0.0005); however the association was attenuated (P = 0.0469) after conditioning on the GWAS index single nucleotide polymorphism (SNP). A  PLEKHA7  intronic variant was the strongest DBP association (rs12806040, MAF = 0.007, P = 0.0006) and was not in LD (r 2  = 0.01) with the GWAS SNP. A  CACNB2  intronic SNP, rs1571787, was the most significant association with PP (MAF = 0.27, P = 0.0003), but was not independent from the GWAS SNP (r 2  = 0.34). Three variants (rs6163 and rs743572 in the  CYP17A1  region and rs112467382 in  PLEKHA7 ) were associated with BP traits (P<0.001). Rare variation, aggregately assessed in the 6 regions, was not significantly associated with BP measures.    Conclusion  Six targeted gene regions, previously identified by GWAS, did not harbor novel variation with large effects on BP in this sample.

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Sequence Analysis of Six Blood Pressure Candidate Regions in 4,178 Individuals: The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Targeted Sequencing Study