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Genome-wide meta-analysis of SNP and antihypertensive medication interactions on left ventricular traits in African Americans.

TitleGenome-wide meta-analysis of SNP and antihypertensive medication interactions on left ventricular traits in African Americans.
Publication TypeJournal Article
Year of Publication2019
AuthorsDo, 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
JournalMol Genet Genomic Med
Volume7
Issue10
Paginatione00788
Date Published2019 10
ISSN2324-9269
KeywordsAfrican 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>
DOI10.1002/mgg3.788
Alternate JournalMol Genet Genomic Med
PubMed ID31407531
PubMed Central IDPMC6785453
Grant ListHHSN268201300046C / 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