Identification of 15 novel risk loci for coronary artery disease and genetic risk of recurrent events, atrial fibrillation and heart failure
Abstract Coronary artery disease (CAD) is the major cause of morbidity and mortality in the world. Identification of novel genetic determinants may provide new opportunities for developing innovative strategies to predict, prevent and treat CAD. Therefore, we meta-analyzed independent genetic varian...
Guardado en:
| Autores principales: | , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/4107acb79015454cb116fba21d4c248d |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:4107acb79015454cb116fba21d4c248d |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:4107acb79015454cb116fba21d4c248d2021-12-02T15:06:05ZIdentification of 15 novel risk loci for coronary artery disease and genetic risk of recurrent events, atrial fibrillation and heart failure10.1038/s41598-017-03062-82045-2322https://doaj.org/article/4107acb79015454cb116fba21d4c248d2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03062-8https://doaj.org/toc/2045-2322Abstract Coronary artery disease (CAD) is the major cause of morbidity and mortality in the world. Identification of novel genetic determinants may provide new opportunities for developing innovative strategies to predict, prevent and treat CAD. Therefore, we meta-analyzed independent genetic variants passing P <× 10−5 in CARDIoGRAMplusC4D with novel data made available by UK Biobank. Of the 161 genetic variants studied, 71 reached genome wide significance (p < 5 × 10−8) including 15 novel loci. These novel loci include multiple genes that are involved in angiogenesis (TGFB1, ITGB5, CDH13 and RHOA) and 2 independent variants in the TGFB1 locus. We also identified SGEF as a candidate gene in one of the novel CAD loci. SGEF was previously suggested as a therapeutic target based on mouse studies. The genetic risk score of CAD predicted recurrent CAD events and cardiovascular mortality. We also identified significant genetic correlations between CAD and other cardiovascular conditions, including heart failure and atrial fibrillation. In conclusion, we substantially increased the number of loci convincingly associated with CAD and provide additional biological and clinical insights.Niek VerweijRuben N. EppingaYanick HagemeijerPim van der HarstNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Niek Verweij Ruben N. Eppinga Yanick Hagemeijer Pim van der Harst Identification of 15 novel risk loci for coronary artery disease and genetic risk of recurrent events, atrial fibrillation and heart failure |
| description |
Abstract Coronary artery disease (CAD) is the major cause of morbidity and mortality in the world. Identification of novel genetic determinants may provide new opportunities for developing innovative strategies to predict, prevent and treat CAD. Therefore, we meta-analyzed independent genetic variants passing P <× 10−5 in CARDIoGRAMplusC4D with novel data made available by UK Biobank. Of the 161 genetic variants studied, 71 reached genome wide significance (p < 5 × 10−8) including 15 novel loci. These novel loci include multiple genes that are involved in angiogenesis (TGFB1, ITGB5, CDH13 and RHOA) and 2 independent variants in the TGFB1 locus. We also identified SGEF as a candidate gene in one of the novel CAD loci. SGEF was previously suggested as a therapeutic target based on mouse studies. The genetic risk score of CAD predicted recurrent CAD events and cardiovascular mortality. We also identified significant genetic correlations between CAD and other cardiovascular conditions, including heart failure and atrial fibrillation. In conclusion, we substantially increased the number of loci convincingly associated with CAD and provide additional biological and clinical insights. |
| format |
article |
| author |
Niek Verweij Ruben N. Eppinga Yanick Hagemeijer Pim van der Harst |
| author_facet |
Niek Verweij Ruben N. Eppinga Yanick Hagemeijer Pim van der Harst |
| author_sort |
Niek Verweij |
| title |
Identification of 15 novel risk loci for coronary artery disease and genetic risk of recurrent events, atrial fibrillation and heart failure |
| title_short |
Identification of 15 novel risk loci for coronary artery disease and genetic risk of recurrent events, atrial fibrillation and heart failure |
| title_full |
Identification of 15 novel risk loci for coronary artery disease and genetic risk of recurrent events, atrial fibrillation and heart failure |
| title_fullStr |
Identification of 15 novel risk loci for coronary artery disease and genetic risk of recurrent events, atrial fibrillation and heart failure |
| title_full_unstemmed |
Identification of 15 novel risk loci for coronary artery disease and genetic risk of recurrent events, atrial fibrillation and heart failure |
| title_sort |
identification of 15 novel risk loci for coronary artery disease and genetic risk of recurrent events, atrial fibrillation and heart failure |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/4107acb79015454cb116fba21d4c248d |
| work_keys_str_mv |
AT niekverweij identificationof15novelrisklociforcoronaryarterydiseaseandgeneticriskofrecurrenteventsatrialfibrillationandheartfailure AT rubenneppinga identificationof15novelrisklociforcoronaryarterydiseaseandgeneticriskofrecurrenteventsatrialfibrillationandheartfailure AT yanickhagemeijer identificationof15novelrisklociforcoronaryarterydiseaseandgeneticriskofrecurrenteventsatrialfibrillationandheartfailure AT pimvanderharst identificationof15novelrisklociforcoronaryarterydiseaseandgeneticriskofrecurrenteventsatrialfibrillationandheartfailure |
| _version_ |
1718388577524514816 |