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
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 pre...
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| Published in: | PloS one Vol. 9; no. 10; p. e109155 |
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| Main Authors: | , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Public Library of Science
02.10.2014
Public Library of Science (PLoS) |
| Subjects: | |
| ISSN: | 1932-6203, 1932-6203 |
| Online Access: | Get full text |
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| Summary: | 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).
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.
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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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 Competing Interests: The authors have read the journal's policy and an author of this manuscript has the following competing interests: Dr. Psaty serves on the DSMB for a clinical trial of a device funded by the manufacturer (Zoll LifeCor), and on the Steering Committee for the Yale Open-Data Access Project funded by Medtronic. Dr. Psaty, co-author, has indicated a potential competing interest for the purpose of transparency, but this disclosure does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. Conceived and designed the experiments: RAG EB BMP AC DL. Performed the experiments: DM RAG. Analyzed the data: ACM JCB SJH. Contributed reagents/materials/analysis tools: TL KR. Wrote the paper: ACM JCB SJH GBE. Determined the regions for targeted sequencing: GBE. ACM, JB, and SJH are joint first authors on this work. |
| ISSN: | 1932-6203 1932-6203 |
| DOI: | 10.1371/journal.pone.0109155 |