A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough

J. D. Mosley; C. M. Shaffer; S. L. van Driest; P. E. Weeke; Q. S. Wells; J. H. Karnes; D. R. Velez Edwards; W.-Q. Wei; P. L. Teixeira; L. Bastarache; D. C. Crawford; R. Li; T. A. Manolio; E. P. Bottinger; C. A. McCarty; J. G. Linneman; M. H. Brilliant; J. A. Pacheco; W. Thompson; R. L. Chisholm; G. P. Jarvik; D. R. Crosslin; D. S. Carrell; E. Baldwin; J. Ralston; E. B. Larson; J. Grafton; A. Scrol; H. Jouni; I. J. Kullo; G. Tromp; K. M. Borthwick; H. Kuivaniemi; D. J. Carey; M. D. Ritchie; Y. Bradford; S. S. Verma; C. G. Chute; A. Veluchamy; M. K. Siddiqui; C. N. A. Palmer; A. Doney; S. H. Mahmoudpour; A. H. Maitland-van der Zee; A. D. Morris; J. C. Denny; D. M. Roden

doi:https://doi.org/10.1038/tpj.2015.51

A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough

J. D. Mosley, C. M. Shaffer, S. L. van Driest, P. E. Weeke, Q. S. Wells, J. H. Karnes, D. R. Velez Edwards, W.-Q. Wei, P. L. Teixeira, L. Bastarache, D. C. Crawford, R. Li, T. A. Manolio, E. P. Bottinger, C. A. McCarty, J. G. Linneman, M. H. Brilliant, J. A. Pacheco, W. Thompson, R. L. ChisholmG. P. Jarvik, D. R. Crosslin, D. S. Carrell, E. Baldwin, J. Ralston, E. B. Larson, J. Grafton, A. Scrol, H. Jouni, I. J. Kullo, G. Tromp, K. M. Borthwick, H. Kuivaniemi, D. J. Carey, M. D. Ritchie, Y. Bradford, S. S. Verma, C. G. Chute, A. Veluchamy, M. K. Siddiqui, C. N. A. Palmer, A. Doney, S. H. Mahmoudpour, A. H. Maitland-van der Zee, A. D. Morris, J. C. Denny, D. M. Roden

Pulmonology (AMC)

Research output: Contribution to journal › Article › Academic › peer-review

41 Citations (Scopus)

Abstract

The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency = 0.33, odds ratio (OR) = 1.3 (95% confidence interval (CI): 1.2-1.4), P = 1.0 x 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n = 926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n = 4309). Replication was observed at rs7675300 (OR = 1.32 (1.01-1.70), P = 0.04) in eMERGE and at rs16870989 and rs1495509 (OR = 1.15 (1.01-1.30), P = 0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR = 1.23 (1.15-1.32), P = 1.9 x 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk

Original language	English
Pages (from-to)	231-237
Journal	pharmacogenomics journal
Volume	16
Issue number	3
DOIs	https://doi.org/10.1038/tpj.2015.51
Publication status	Published - 2016

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https://doi.org/10.1038/tpj.2015.51

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Mosley, J. D., Shaffer, C. M., van Driest, S. L., Weeke, P. E., Wells, Q. S., Karnes, J. H., Velez Edwards, D. R., Wei, W.-Q., Teixeira, P. L., Bastarache, L., Crawford, D. C., Li, R., Manolio, T. A., Bottinger, E. P., McCarty, C. A., Linneman, J. G., Brilliant, M. H., Pacheco, J. A., Thompson, W., ... Roden, D. M. (2016). A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough. pharmacogenomics journal, 16(3), 231-237. https://doi.org/10.1038/tpj.2015.51

@article{e57b53377f9240f5bfac798b543f8cf7,

title = "A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough",

abstract = "The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency = 0.33, odds ratio (OR) = 1.3 (95% confidence interval (CI): 1.2-1.4), P = 1.0 x 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n = 926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n = 4309). Replication was observed at rs7675300 (OR = 1.32 (1.01-1.70), P = 0.04) in eMERGE and at rs16870989 and rs1495509 (OR = 1.15 (1.01-1.30), P = 0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR = 1.23 (1.15-1.32), P = 1.9 x 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk",

author = "Mosley, {J. D.} and Shaffer, {C. M.} and {van Driest}, {S. L.} and Weeke, {P. E.} and Wells, {Q. S.} and Karnes, {J. H.} and {Velez Edwards}, {D. R.} and W.-Q. Wei and Teixeira, {P. L.} and L. Bastarache and Crawford, {D. C.} and R. Li and Manolio, {T. A.} and Bottinger, {E. P.} and McCarty, {C. A.} and Linneman, {J. G.} and Brilliant, {M. H.} and Pacheco, {J. A.} and W. Thompson and Chisholm, {R. L.} and Jarvik, {G. P.} and Crosslin, {D. R.} and Carrell, {D. S.} and E. Baldwin and J. Ralston and Larson, {E. B.} and J. Grafton and A. Scrol and H. Jouni and Kullo, {I. J.} and G. Tromp and Borthwick, {K. M.} and H. Kuivaniemi and Carey, {D. J.} and Ritchie, {M. D.} and Y. Bradford and Verma, {S. S.} and Chute, {C. G.} and A. Veluchamy and Siddiqui, {M. K.} and Palmer, {C. N. A.} and A. Doney and Mahmoudpour, {S. H.} and {Maitland-van der Zee}, {A. H.} and Morris, {A. D.} and Denny, {J. C.} and Roden, {D. M.}",

year = "2016",

doi = "https://doi.org/10.1038/tpj.2015.51",

language = "English",

volume = "16",

pages = "231--237",

journal = "pharmacogenomics journal",

issn = "1470-269X",

publisher = "Nature Publishing Group",

number = "3",

}

Mosley, JD, Shaffer, CM, van Driest, SL, Weeke, PE, Wells, QS, Karnes, JH, Velez Edwards, DR, Wei, W-Q, Teixeira, PL, Bastarache, L, Crawford, DC, Li, R, Manolio, TA, Bottinger, EP, McCarty, CA, Linneman, JG, Brilliant, MH, Pacheco, JA, Thompson, W, Chisholm, RL, Jarvik, GP, Crosslin, DR, Carrell, DS, Baldwin, E, Ralston, J, Larson, EB, Grafton, J, Scrol, A, Jouni, H, Kullo, IJ, Tromp, G, Borthwick, KM, Kuivaniemi, H, Carey, DJ, Ritchie, MD, Bradford, Y, Verma, SS, Chute, CG, Veluchamy, A, Siddiqui, MK, Palmer, CNA, Doney, A, Mahmoudpour, SH, Maitland-van der Zee, AH, Morris, AD, Denny, JC & Roden, DM 2016, 'A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough', pharmacogenomics journal, vol. 16, no. 3, pp. 231-237. https://doi.org/10.1038/tpj.2015.51

TY - JOUR

T1 - A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough

AU - Mosley, J. D.

AU - Shaffer, C. M.

AU - van Driest, S. L.

AU - Weeke, P. E.

AU - Wells, Q. S.

AU - Karnes, J. H.

AU - Velez Edwards, D. R.

AU - Wei, W.-Q.

AU - Teixeira, P. L.

AU - Bastarache, L.

AU - Crawford, D. C.

AU - Li, R.

AU - Manolio, T. A.

AU - Bottinger, E. P.

AU - McCarty, C. A.

AU - Linneman, J. G.

AU - Brilliant, M. H.

AU - Pacheco, J. A.

AU - Thompson, W.

AU - Chisholm, R. L.

AU - Jarvik, G. P.

AU - Crosslin, D. R.

AU - Carrell, D. S.

AU - Baldwin, E.

AU - Ralston, J.

AU - Larson, E. B.

AU - Grafton, J.

AU - Scrol, A.

AU - Jouni, H.

AU - Kullo, I. J.

AU - Tromp, G.

AU - Borthwick, K. M.

AU - Kuivaniemi, H.

AU - Carey, D. J.

AU - Ritchie, M. D.

AU - Bradford, Y.

AU - Verma, S. S.

AU - Chute, C. G.

AU - Veluchamy, A.

AU - Siddiqui, M. K.

AU - Palmer, C. N. A.

AU - Doney, A.

AU - Mahmoudpour, S. H.

AU - Maitland-van der Zee, A. H.

AU - Morris, A. D.

AU - Denny, J. C.

AU - Roden, D. M.

PY - 2016

Y1 - 2016

N2 - The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency = 0.33, odds ratio (OR) = 1.3 (95% confidence interval (CI): 1.2-1.4), P = 1.0 x 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n = 926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n = 4309). Replication was observed at rs7675300 (OR = 1.32 (1.01-1.70), P = 0.04) in eMERGE and at rs16870989 and rs1495509 (OR = 1.15 (1.01-1.30), P = 0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR = 1.23 (1.15-1.32), P = 1.9 x 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk

AB - The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency = 0.33, odds ratio (OR) = 1.3 (95% confidence interval (CI): 1.2-1.4), P = 1.0 x 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n = 926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n = 4309). Replication was observed at rs7675300 (OR = 1.32 (1.01-1.70), P = 0.04) in eMERGE and at rs16870989 and rs1495509 (OR = 1.15 (1.01-1.30), P = 0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR = 1.23 (1.15-1.32), P = 1.9 x 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk

U2 - https://doi.org/10.1038/tpj.2015.51

DO - https://doi.org/10.1038/tpj.2015.51

M3 - Article

C2 - 26169577

SN - 1470-269X

VL - 16

SP - 231

EP - 237

JO - pharmacogenomics journal

JF - pharmacogenomics journal

IS - 3

ER -