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Genome-wide meta-analysis of SNP and antihypertensive medication interactions on left ventricular traits in African Americans.
Tuesday,2020-10-27 18:33 America/Los_Angeles — ecterry
| Title | Genome-wide meta-analysis of SNP and antihypertensive medication interactions on left ventricular traits in African Americans. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | Do, AN, Zhao, W, Baldridge, AS, Raffield, LM, Wiggins, KL, Shah, SJ, Aslibekyan, S, Tiwari, HK, Limdi, N, Zhi, D, Sitlani, CM, Taylor, KD, Psaty, BM, Sotoodehnia, N, Brody, JA, Rasmussen-Torvik, LJ, Lloyd-Jones, D, Lange, LA, Wilson, JG, Smith, JA, Kardia, SLR, Mosley, TH, Vasan, RS, Arnett, DK, Irvin, MR |
| Journal | Mol Genet Genomic Med |
| Volume | 7 |
| Issue | 10 |
| Pagination | e00788 |
| Date Published | 2019 10 |
| ISSN | 2324-9269 |
| Keywords | African Americans, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Calcium Channel Blockers, Humans, Observational Studies as Topic, Pharmacogenomic Variants, Polymorphism, Single Nucleotide, Sodium Chloride Symporter Inhibitors, Ventricular Dysfunction, Left |
| Abstract | <p><b>BACKGROUND: </b>Left ventricular (LV) hypertrophy affects up to 43% of African Americans (AAs). Antihypertensive treatment reduces LV mass (LVM). However, interindividual variation in LV traits in response to antihypertensive treatments exists. We hypothesized that genetic variants may modify the association of antihypertensive treatment class with LV traits measured by echocardiography.</p><p><b>METHODS: </b>We evaluated the main effects of the three most common antihypertensive treatments for AAs as well as the single nucleotide polymorphism (SNP)-by-drug interaction on LVM and relative wall thickness (RWT) in 2,068 participants across five community-based cohorts. Treatments included thiazide diuretics (TDs), angiotensin converting enzyme inhibitors (ACE-Is), and dihydropyridine calcium channel blockers (dCCBs) and were compared in a pairwise manner. We performed fixed effects inverse variance weighted meta-analyses of main effects of drugs and 2.5 million SNP-by-drug interaction estimates.</p><p><b>RESULTS: </b>We observed that dCCBs versus TDs were associated with higher LVM after adjusting for covariates (p = 0.001). We report three SNPs at a single locus on chromosome 20 that modified the association between RWT and treatment when comparing dCCBs to ACE-Is with consistent effects across cohorts (smallest p = 4.7 × 10 , minor allele frequency range 0.09-0.12). This locus has been linked to LV hypertrophy in a previous study. A marginally significant locus in BICD1 (rs326641) was validated in an external population.</p><p><b>CONCLUSIONS: </b>Our study identified one locus having genome-wide significant SNP-by-drug interaction effect on RWT among dCCB users in comparison to ACE-I users. Upon additional validation in future studies, our findings can enhance the precision of medical approaches in hypertension treatment.</p> |
| DOI | 10.1002/mgg3.788 |
| Alternate Journal | Mol Genet Genomic Med |
| PubMed ID | 31407531 |
| PubMed Central ID | PMC6785453 |
| Grant List | HHSN268201300046C / HL / NHLBI NIH HHS / United States U01-HG04424 / / NHGRI Gene Environment Association Studies (GENEVA) / International N01HC85081 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States HHSN268201300026C / HL / NHLBI NIH HHS / United States R01HL103612 / / National Heart, Lung, and Blood Institute (NHLBI) / International HHSN268201300027C / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268201300050C / HL / NHLBI NIH HHS / United States HHSN268201300025C / HL / NHLBI NIH HHS / United States U01HL080295 / / National Heart, Lung, and Blood Institute (NHLBI) / International N01HC85084 / / National Heart, Lung, and Blood Institute (NHLBI) / International HHSN268201300029C / HL / NHLBI NIH HHS / United States R01HL085251 / / National Heart, Lung, and Blood Institute (NHLBI) / International R01HL087652 / / National Heart, Lung, and Blood Institute (NHLBI) / International N01HC55222 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States HHSN268200960009C / / National Heart, Lung, and Blood Institute (NHLBI) / International UL1TR000124 / / National Center for Advancing Translational Sciences, CTSI / International HHSN268201300047C / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States HHSN268200900041C / HL / NHLBI NIH HHS / United States T32 HL129982 / HL / NHLBI NIH HHS / United States HHSN268201300049C / HL / NHLBI NIH HHS / United States N01HC35129 / / National Heart, Lung, and Blood Institute (NHLBI) / International HHSN268201300048C / HL / NHLBI NIH HHS / United States U01-HG004729 / / NHGRI Gene Environment Association Studies (GENEVA) / International R01HL105756 / / National Heart, Lung, and Blood Institute (NHLBI) / International R01HL120393 / / National Heart, Lung, and Blood Institute (NHLBI) / International U01-HG004446 / / NHGRI Gene Environment Association Studies (GENEVA) / International HHSN268200800007C / HL / NHLBI NIH HHS / United States R01 HL55673 / / National Heart, Lung, and Blood Institute (NHLBI) / International R01HL130114 / / National Heart, Lung, and Blood Institute (NHLBI) / International N01-HC-65226 / / NHLBI Candidate-Gene Association Resource / International HHSN268201300028C / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States |
ePub date:
19/08