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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.
Wednesday,2015-03-04 15:39 America/Los_Angeles — zdrager
| Title | 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. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Morrison, AC, Bis, JC, Hwang, S-J, Ehret, GB, Lumley, T, Rice, K, Muzny, D, Gibbs, RA, Boerwinkle, E, Psaty, BM, Chakravarti, A, Levy, D |
| Journal | PLoS One |
| Volume | 9 |
| Issue | 10 |
| Pagination | e109155 |
| Date Published | 2014 |
| ISSN | 1932-6203 |
| Keywords | Aging, Blood Pressure, Cohort Studies, Heart, Humans, Sequence Analysis |
| Abstract | <p><b>BACKGROUND: </b>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).</p><p><b>METHODS AND RESULTS: </b>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.</p><p><b>CONCLUSION: </b>Six targeted gene regions, previously identified by GWAS, did not harbor novel variation with large effects on BP in this sample.</p> |
| DOI | 10.1371/journal.pone.0109155 |
| Alternate Journal | PLoS ONE |
| PubMed ID | 25275628 |
| PubMed Central ID | PMC4183565 |
| Grant List | 5RC2HL102419 / HL / NHLBI NIH HHS / United States AG-023629 / AG / NIA NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States AG-15928 / AG / NIA NIH HHS / United States AG-20098 / AG / NIA NIH HHS / United States HHSN268201100005C / / PHS HHS / United States HHSN268201100006C / / PHS HHS / United States HHSN268201100007C / / PHS HHS / United States HHSN268201100008C / / PHS HHS / United States HHSN268201100009C / / PHS HHS / United States HHSN268201100010C / / PHS HHS / United States HHSN268201100011C / / PHS HHS / United States HHSN268201100012C / / PHS HHS / United States HHSN268201200036C / / PHS HHS / United States HL080295 / HL / NHLBI NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States HL105756 / HL / NHLBI NIH HHS / United States N01 HC-15103 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01-HC-85239 / HC / NHLBI NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States U54 HG003273 / HG / NHGRI NIH HHS / United States |