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A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough
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 diagn...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group
2016
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713364/ https://www.ncbi.nlm.nih.gov/pubmed/26169577 http://dx.doi.org/10.1038/tpj.2015.51 |
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| author | 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 Chisholm, R L Jarvik, G P Crosslin, D R Carrell, D S Baldwin, E Ralston, J Larson, E B Grafton, J Scrol, A Jouni, H Kullo, I J Tromp, G Borthwick, K M Kuivaniemi, H Carey, D J Ritchie, M D Bradford, Y Verma, S S Chute, C G Veluchamy, A Siddiqui, M K Palmer, C N A Doney, A MahmoudPour, S H Maitland-van der Zee, A H Morris, A D Denny, J C Roden, D M |
| author_facet | 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 Chisholm, R L Jarvik, G P Crosslin, D R Carrell, D S Baldwin, E Ralston, J Larson, E B Grafton, J Scrol, A Jouni, H Kullo, I J Tromp, G Borthwick, K M Kuivaniemi, H Carey, D J Ritchie, M D Bradford, Y Verma, S S Chute, C G Veluchamy, A Siddiqui, M K Palmer, C N A Doney, A MahmoudPour, S H Maitland-van der Zee, A H Morris, A D Denny, J C Roden, D M |
| author_sort | Mosley, J D |
| collection | PubMed |
| description | 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 × 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 × 10(−9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk. |
| format | Online Article Text |
| id | pubmed-4713364 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-47133642016-05-24 A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough 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 Chisholm, R L Jarvik, G P Crosslin, D R Carrell, D S Baldwin, E Ralston, J Larson, E B Grafton, J Scrol, A Jouni, H Kullo, I J Tromp, G Borthwick, K M Kuivaniemi, H Carey, D J Ritchie, M D Bradford, Y Verma, S S Chute, C G Veluchamy, A Siddiqui, M K Palmer, C N A Doney, A MahmoudPour, S H Maitland-van der Zee, A H Morris, A D Denny, J C Roden, D M Pharmacogenomics J Original Article 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 × 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 × 10(−9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk. Nature Publishing Group 2016-06 2015-07-14 /pmc/articles/PMC4713364/ /pubmed/26169577 http://dx.doi.org/10.1038/tpj.2015.51 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article‘s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| spellingShingle | Original Article 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 Chisholm, R L Jarvik, G P Crosslin, D R Carrell, D S Baldwin, E Ralston, J Larson, E B Grafton, J Scrol, A Jouni, H Kullo, I J Tromp, G Borthwick, K M Kuivaniemi, H Carey, D J Ritchie, M D Bradford, Y Verma, S S Chute, C G Veluchamy, A Siddiqui, M K Palmer, C N A Doney, A MahmoudPour, S H Maitland-van der Zee, A H Morris, A D Denny, J C Roden, D M A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough |
| title | A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough |
| title_full | A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough |
| title_fullStr | A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough |
| title_full_unstemmed | A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough |
| title_short | A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough |
| title_sort | genome-wide association study identifies variants in kcnip4 associated with ace inhibitor-induced cough |
| topic | Original Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713364/ https://www.ncbi.nlm.nih.gov/pubmed/26169577 http://dx.doi.org/10.1038/tpj.2015.51 |
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