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
Year: 2014
Type: article
Study design: Observational Study
Abstract: 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.
Source: PLoS ONE
Institutions: The University of Texas Health Science Center at Houston, University of Washington, National Institutes of Health, National Heart, Lung, and Blood Institute, Framingham Heart Study, Johns Hopkins University, Johns Hopkins Medicine, University Hospital of Geneva, University of Auckland, Baylor College of Medicine, Group Health Cooperative, Kaiser Permanente Washington Health Research Institute
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G1023702118, G1052397333, G10717269, G1097528416, G1135917780, G1220223050, G1224608327, G1243299691, G125972088, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G1401438683, G1412333385, G1438302022, G1460387277, CHS-ULTRASOUND READING, G1527150935, CORONARY HEART DISEASE AND STROKE, MRI READING CENTER FOR THE CARDIOVASCULAR HEALTH STUDY, G1691174148, G1727292203, G173303992, G1742450553, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, G1890355377, G1909643007, G1941623656, G2125948122, G2193588257, G2194386449, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G236442059, G2391884931, G250621538, Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), G2555954497, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G270907595, G274585943, G277826483, G2786044735, G2800149121, G2818629771, G2847759872, G2882309788, G2918387404, G301743239, G3045517347, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G3114902838, G3137375862, G3145043064, G3152385821, G3169706684, G3205625555, G328935669, G3370719899, G3410686264, G34347772, G3462919067, G3507024915, G3560915123, G36937976, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, Predictors of Alheimers Disease in Mild Cognitive Impairment, G4012114008, G4048755144, G4167445418, G4200864717, G423252844, The Human Genome Sequencing Center, G457330776, G4617276643, G4622379297, G4660668308, G4987078009, G5053595415, G5074086979, G5164707915, G5167412771, G5281659474, G5386252567, G5479317095, G567847597, G573134505, G581887176, CHARGE consortium: omics discovery for CVD and aging phenotypes, CHS Events Follow-up Study, G61834786, G6195637971, G6226795708, Predictors of Alzheimers Disease in Mild Cognitive Impairment, G6361934619, The Framingham Heart Study, G6548750934, G6552090923, G6832344490, G687544517, G693548699, G7035200923, G7176672723, G7217924807, G7505613430, CHS RETINAL READING CENTER, G764651519, CARDIOVASCULAR HEALTH STUDY--ECHOCARDIOGRAPHY, G766700449, G766843672, Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), G777822606, CHS Events Follow-up Study, G7999488110, G80149192, G806768229, G8068269535, G8260701975, G8402048158, COGNITIVE TESTS, APOE, BRAIN MRI AND RISKS OF DEMENTIA, G8593276544, G859984287, CHS-Transition Phase -268055222, Hormonal trajectories in aging, G8892155751, Building on GWAS for NHLBI-disease: the CHARGE consortium, G9000027259, G9000065537, G9000069887, G9000124008, G9000124674, G9000143860, G9000145448, G9000155215, G9000155493, G9000159977, G9000239991, G9000294005, G905887895, G936067872, G960597250
OpenAlex ID: W1993080870