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Genome-Wide Association Study of Apparent Treatment-Resistant Hypertension in the CHARGE Consortium: The CHARGE Pharmacogenetics Working Group.
Thursday,2023-06-15 12:34 America/Los_Angeles — ecterry
| Title | Genome-Wide Association Study of Apparent Treatment-Resistant Hypertension in the CHARGE Consortium: The CHARGE Pharmacogenetics Working Group. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | Irvin, MR, Sitlani, CM, Floyd, JS, Psaty, BM, Bis, JC, Wiggins, KL, Whitsel, EA, Stürmer, T, Stewart, J, Raffield, L, Sun, F, Liu, C-T, Xu, H, Cupples, AL, Tanner, RM, Rossing, P, Smith, A, Zilhão, NR, Launer, LJ, Noordam, R, Rotter, JI, Yao, J, Li, X, Guo, X, Limdi, N, Sundaresan, A, Lange, L, Correa, A, Stott, DJ, Ford, I, J Jukema, W, Gudnason, V, Mook-Kanamori, DO, Trompet, S, Palmas, W, Warren, HR, Hellwege, JN, Giri, A, O'donnell, C, Hung, AM, Edwards, TL, Ahluwalia, TS, Arnett, DK, Avery, CL |
| Journal | Am J Hypertens |
| Volume | 32 |
| Issue | 12 |
| Pagination | 1146-1153 |
| Date Published | 2019 Nov 15 |
| ISSN | 1941-7225 |
| Keywords | Aged, Antihypertensive Agents, Black or African American, Blood Pressure, Case-Control Studies, DNA (Cytosine-5-)-Methyltransferases, DNA Methyltransferase 3A, DNA-Binding Proteins, Drug Resistance, Dystrophin-Associated Proteins, Europe, Female, Genetic Loci, Genome-Wide Association Study, Humans, Hypertension, Male, Middle Aged, Myosin Heavy Chains, Myosin Type V, Neuropeptides, Pharmacogenetics, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, Transcription Factors, United States, White People |
| Abstract | <p><b>BACKGROUND: </b>Only a handful of genetic discovery efforts in apparent treatment-resistant hypertension (aTRH) have been described.</p><p><b>METHODS: </b>We conducted a case-control genome-wide association study of aTRH among persons treated for hypertension, using data from 10 cohorts of European ancestry (EA) and 5 cohorts of African ancestry (AA). Cases were treated with 3 different antihypertensive medication classes and had blood pressure (BP) above goal (systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg) or 4 or more medication classes regardless of BP control (nEA = 931, nAA = 228). Both a normotensive control group and a treatment-responsive control group were considered in separate analyses. Normotensive controls were untreated (nEA = 14,210, nAA = 2,480) and had systolic BP/diastolic BP < 140/90 mm Hg. Treatment-responsive controls (nEA = 5,266, nAA = 1,817) had BP at goal (<140/90 mm Hg), while treated with one antihypertensive medication class. Individual cohorts used logistic regression with adjustment for age, sex, study site, and principal components for ancestry to examine the association of single-nucleotide polymorphisms with case-control status. Inverse variance-weighted fixed-effects meta-analyses were carried out using METAL.</p><p><b>RESULTS: </b>The known hypertension locus, CASZ1, was a top finding among EAs (P = 1.1 × 10-8) and in the race-combined analysis (P = 1.5 × 10-9) using the normotensive control group (rs12046278, odds ratio = 0.71 (95% confidence interval: 0.6-0.8)). Single-nucleotide polymorphisms in this locus were robustly replicated in the Million Veterans Program (MVP) study in consideration of a treatment-responsive control group. There were no statistically significant findings for the discovery analyses including treatment-responsive controls.</p><p><b>CONCLUSION: </b>This genomic discovery effort for aTRH identified CASZ1 as an aTRH risk locus.</p> |
| DOI | 10.1093/ajh/hpz150 |
| Alternate Journal | Am J Hypertens |
| PubMed ID | 31545351 |
| PubMed Central ID | PMC6856621 |
| Grant List | R01 HL120393 / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States HHSN268201800014I / HB / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States P30 DK079626 / DK / NIDDK NIH HHS / United States HHSN268201800014C / HL / NHLBI NIH HHS / United States K24 HL133373 / HL / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States HHSN268201800013I / MD / NIMHD NIH HHS / United States S10 OD023680 / OD / NIH HHS / United States K12 HD043483 / HD / NICHD NIH HHS / United States HHSN268201800015I / HB / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 HL073410 / HL / NHLBI NIH HHS / United States RES 13-457 / RD / ORD VA / United States U01 HL120393 / HL / NHLBI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States K08 HL116640 / HL / NHLBI NIH HHS / United States |
ePub date:
19/11