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Genome-wide meta-analysis of SNP-by9-ACEI/ARB and SNP-by-thiazide diuretic and effect on serum potassium in cohorts of European and African ancestry.
Wednesday,2018-09-19 10:27 America/Los_Angeles — ecterry
| Title | Genome-wide meta-analysis of SNP-by9-ACEI/ARB and SNP-by-thiazide diuretic and effect on serum potassium in cohorts of European and African ancestry. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Irvin, MR, Sitlani, CM, Noordam, R, Avery, CL, Bis, JC, Floyd, JS, Li, J, Limdi, NA, Srinivasasainagendra, V, Stewart, J, de Mutsert, R, Mook-Kanamori, DO, Lipovich, L, Kleinbrink, EL, Smith, A, Bartz, TM, Whitsel, EA, Uitterlinden, AG, Wiggins, KL, Wilson, JG, Zhi, D, Stricker, BH, Rotter, JI, Arnett, DK, Psaty, BM, Lange, LA |
| Journal | Pharmacogenomics J |
| Date Published | 2018 Jun 01 |
| ISSN | 1473-1150 |
| Abstract | <p>We evaluated interactions of SNP-by-ACE-I/ARB and SNP-by-TD on serum potassium (K+) among users of antihypertensive treatments (anti-HTN). Our study included seven European-ancestry (EA) (N = 4835) and four African-ancestry (AA) cohorts (N = 2016). We performed race-stratified, fixed-effect, inverse-variance-weighted meta-analyses of 2.5 million SNP-by-drug interaction estimates; race-combined meta-analysis; and trans-ethnic fine-mapping. Among EAs, we identified 11 significant SNPs (P < 5 × 10) for SNP-ACE-I/ARB interactions on serum K+ that were located between NR2F1-AS1 and ARRDC3-AS1 on chromosome 5 (top SNP rs6878413 P = 1.7 × 10; ratio of serum K+ in ACE-I/ARB exposed compared to unexposed is 1.0476, 1.0280, 1.0088 for the TT, AT, and AA genotypes, respectively). Trans-ethnic fine mapping identified the same group of SNPs on chromosome 5 as genome-wide significant for the ACE-I/ARB analysis. In conclusion, SNP-by-ACE-I /ARB interaction analyses uncovered loci that, if replicated, could have future implications for the prevention of arrhythmias due to anti-HTN treatment-related hyperkalemia. Before these loci can be identified as clinically relevant, future validation studies of equal or greater size in comparison to our discovery effort are needed.</p> |
| DOI | 10.1038/s41397-018-0021-9 |
| Alternate Journal | Pharmacogenomics J. |
| PubMed ID | 29855607 |
| Grant List | U01 HL054471 / HL / NHLBI NIH HHS / United States R01 HL103612 / HL / NHLBI NIH HHS / United States N01 HC085083 / HC / WHI NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States U10 HL054509 / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01 HC085086 / HC / WHI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States R01 HL085251 / HL / NHLBI NIH HHS / United States N01 HC085082 / HC / WHI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States R01 HL087652 / 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 P30 DK063491 / DK / NIDDK NIH HHS / United States N01 HC085080 / HC / WHI NIH HHS / United States N01 HC085079 / HC / WHI NIH HHS / United States N01 HC085081 / HC / WHI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States R01 HL073410 / HL / NHLBI NIH HHS / United States R01 HL055673 / HL / NHLBI NIH HHS / United States |
ePub date:
18/06