Key result
Targeted sequencing of six blood pressure loci previously identified by GWAS did not identify novel common or rare variants with large effects on blood pressure traits.
Cohort (n=4,178)
Yes
Targeted sequencing of six GWAS-identified blood pressure loci did not reveal novel rare or common variants with large effects on blood pressure traits.
Answers are grounded in this paper and cite their sources.
Null sequencing results at six loci do not support clinical variant screening; leaves open broader genomic or polygenic contributions to blood pressure.
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 (r² = 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 (r² = 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.
No takes yet. Share an insight, caveat, or question.
Morrison et al. (2014) conducted a cohort in Blood pressure (SBP, DBP, PP, MAP) (n=4,178). Sequence variation in six blood pressure candidate genes (ATP2B1, CACNB2, CYP17A1, JAG1, PLEKHA7, SH2B3) vs. Reference alleles was evaluated on Association of common and rare variants with blood pressure traits (SBP, DBP, PP, MAP). Targeted sequencing of six blood pressure loci previously identified by GWAS did not identify novel common or rare variants with large effects on blood pressure traits.
Synapse has enriched 10 related papers. Consider them for comparative context: