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Whole genome sequence analysis of apparent treatment resistant hypertension status in participants from the Trans-Omics for Precision Medicine program.
Thursday,2024-02-01 21:15 America/Los_Angeles — ecterry
| Title | Whole genome sequence analysis of apparent treatment resistant hypertension status in participants from the Trans-Omics for Precision Medicine program. |
| Publication Type | Journal Article |
| Year of Publication | 2023 |
| Authors | Armstrong, ND, Srinivasasainagendra, V, Ammous, F, Assimes, TL, Beitelshees, AL, Brody, J, Cade, BE, Chen, Y-DIda, Chen, H, de Vries, PS, Floyd, JS, Franceschini, N, Guo, X, Hellwege, JN, House, JS, Hwu, C-M, Kardia, SLR, Lange, EM, Lange, LA, McDonough, CW, Montasser, ME, O'Connell, JR, Shuey, MM, Sun, X, Tanner, RM, Wang, Z, Zhao, W, Carson, AP, Edwards, TL, Kelly, TN, Kenny, EE, Kooperberg, C, Loos, RJF, Morrison, AC, Motsinger-Reif, A, Psaty, BM, Rao, DC, Redline, S, Rich, SS, Rotter, JI, Smith, JA, Smith, AV, Irvin, MR, Arnett, DK |
| Journal | Front Genet |
| Volume | 14 |
| Pagination | 1278215 |
| Date Published | 2023 |
| ISSN | 1664-8021 |
| Abstract | <p> Apparent treatment-resistant hypertension (aTRH) is characterized by the use of four or more antihypertensive (AHT) classes to achieve blood pressure (BP) control. In the current study, we conducted single-variant and gene-based analyses of aTRH among individuals from 12 Trans-Omics for Precision Medicine cohorts with whole-genome sequencing data. Cases were defined as individuals treated for hypertension (HTN) taking three different AHT classes, with average systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg, or four or more medications regardless of BP ( = 1,705). A normotensive control group was defined as individuals with BP < 140/90 mmHg ( = 22,079), not on AHT medication. A second control group comprised individuals who were treatment responsive on one AHT medication with BP < 140/ 90 mmHg ( = 5,424). Logistic regression with kinship adjustment using the Scalable and Accurate Implementation of Generalized mixed models (SAIGE) was performed, adjusting for age, sex, and genetic ancestry. We assessed variants using SKAT-O in rare-variant analyses. Single-variant and gene-based tests were conducted in a pooled multi-ethnicity stratum, as well as self-reported ethnic/racial strata (European and African American). One variant in the known HTN locus, , was a top finding in the multi-ethnic analysis ( = 8.23E-07) for the normotensive control group [rs12476527, odds ratio (95% confidence interval) = 0.80 (0.74-0.88)]. This variant was replicated in the Vanderbilt University Medical Center's DNA repository data. Aggregate gene-based signals included the genes and . Additional work validating these loci in larger, more diverse populations, is warranted to determine whether these regions influence the pathobiology of aTRH.</p> |
| DOI | 10.3389/fgene.2023.1278215 |
| Alternate Journal | Front Genet |
| PubMed ID | 38162683 |
| PubMed Central ID | PMC10755672 |
ePub date:
23/12