Genetically determined serum urate levels and cardiovascular and other diseases in UK Biobank cohort: A phenome-wide mendelian randomization study
The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance. A phenome-wide association study (PheWAS) together with a Bayesian analysi...
Uloženo v:
| Vydáno v: | PLoS medicine Ročník 16; číslo 10; s. e1002937 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
United States
Public Library of Science
18.10.2019
Public Library of Science (PLoS) |
| Témata: | |
| ISSN: | 1549-1676, 1549-1277, 1549-1676 |
| On-line přístup: | Získat plný text |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance.
A phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40-69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 × 10-4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization.
In this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities. |
|---|---|
| AbstractList | Background The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance. Methods and findings A phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40–69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 × 10−4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization. Conclusion In this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities. The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance. A phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40-69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 x 10.sup.-4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization. In this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities. The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance. A phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40-69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 × 10-4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization. In this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities. Evropi Theodoratou and colleagues investigate possible mechanisms linking urate with cardiovascular disease. Background The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance. Methods and findings A phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40-69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 x 10.sup.-4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization. Conclusion In this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities. BackgroundThe role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance.Methods and findingsA phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40-69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 × 10-4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization.ConclusionIn this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities. The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance.BACKGROUNDThe role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance.A phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40-69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 × 10-4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization.METHODS AND FINDINGSA phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40-69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 × 10-4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization.In this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities.CONCLUSIONIn this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities. Background The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance. Methods and findings A phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40–69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effects on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabolic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, coronary atherosclerosis, ischemic heart disease, chronic ischemic heart disease, myocardial infarction, and hypercholesterolemia) that were associated with genetically determined serum urate levels after multiple testing correction (p < 3.35 × 10−4). TreeWAS analysis, examining 10,750 ICD-10 diagnostic terms, identified more sub-phenotypes of cardiovascular and cerebrovascular diseases (e.g., angina pectoris, heart failure, cerebral infarction). MR analysis successfully replicated the association with gout, hypertension, heart diseases, and blood lipid levels but indicated the existence of genetic pleiotropy. Sensitivity analyses support an inference that pleiotropic effects of genetic variants on urate and metabolic traits contribute to the observational associations with CVDs. The main limitations of this study relate to possible bias from pleiotropic effects of the considered genetic variants and possible misclassification of cases for mild disease that did not require hospitalization. Conclusion In this study, high serum urate levels were found to be associated with increased risk of different types of cardiac events. The finding of genetic pleiotropy indicates the existence of common upstream pathological elements influencing both urate and metabolic traits, and this may suggest new opportunities and challenges for developing drugs targeting a common mediator that would be beneficial for both the treatment of gout and the prevention of cardiovascular comorbidities. |
| Audience | Academic |
| Author | Varley, Tim Timofeeva, Maria Joshi, Peter Meng, Xiangrui Campbell, Harry Spiliopoulou, Athina Wei, Wei-Qi Yang, Tian Denny, Joshua C. Gifford, Aliya Tzoulaki, Ioanna Li, Xue Theodoratou, Evropi Mckeigue, Paul He, Yazhou |
| AuthorAffiliation | University of Oxford, UNITED KINGDOM 1 Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom 2 Centre for Population Health Sciences, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom 3 Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Medical Research Council, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom 4 Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America 7 Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece 8 Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom 5 Public Health and Intelligence, NHS National Services Scotland, Edinburgh, United Kingdom 6 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingd |
| AuthorAffiliation_xml | – name: University of Oxford, UNITED KINGDOM – name: 4 Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America – name: 1 Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom – name: 7 Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece – name: 2 Centre for Population Health Sciences, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom – name: 8 Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom – name: 3 Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Medical Research Council, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom – name: 5 Public Health and Intelligence, NHS National Services Scotland, Edinburgh, United Kingdom – name: 6 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom |
| Author_xml | – sequence: 1 givenname: Xue orcidid: 0000-0001-6880-2577 surname: Li fullname: Li, Xue – sequence: 2 givenname: Xiangrui orcidid: 0000-0003-4889-4640 surname: Meng fullname: Meng, Xiangrui – sequence: 3 givenname: Yazhou surname: He fullname: He, Yazhou – sequence: 4 givenname: Athina orcidid: 0000-0002-5929-6585 surname: Spiliopoulou fullname: Spiliopoulou, Athina – sequence: 5 givenname: Maria orcidid: 0000-0002-2503-4253 surname: Timofeeva fullname: Timofeeva, Maria – sequence: 6 givenname: Wei-Qi surname: Wei fullname: Wei, Wei-Qi – sequence: 7 givenname: Aliya surname: Gifford fullname: Gifford, Aliya – sequence: 8 givenname: Tian orcidid: 0000-0002-2939-1055 surname: Yang fullname: Yang, Tian – sequence: 9 givenname: Tim surname: Varley fullname: Varley, Tim – sequence: 10 givenname: Ioanna orcidid: 0000-0002-4275-9328 surname: Tzoulaki fullname: Tzoulaki, Ioanna – sequence: 11 givenname: Peter surname: Joshi fullname: Joshi, Peter – sequence: 12 givenname: Joshua C. orcidid: 0000-0002-3049-7332 surname: Denny fullname: Denny, Joshua C. – sequence: 13 givenname: Paul surname: Mckeigue fullname: Mckeigue, Paul – sequence: 14 givenname: Harry orcidid: 0000-0002-6169-6262 surname: Campbell fullname: Campbell, Harry – sequence: 15 givenname: Evropi orcidid: 0000-0001-5887-9132 surname: Theodoratou fullname: Theodoratou, Evropi |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31626644$$D View this record in MEDLINE/PubMed |
| BookMark | eNqVk11rFDEUhgepWFv9B6IBQfRi13xNZqYXQi1ai8WCWm9DZnJmNzWTrEmmWn-Gv9hsu5VuWUQZmAlnnvdNcj52ii3nHRTFI4KnhFXk5Zkfg1N2uhhATwnGtGHVneI-KXkzIaISWzfW28VOjGdLBjf4XrHNiKBCcH6_-HUIDpLplLUXSEOCMBgHGkUI44DGoBIgC-dgI1JOo04Fbfy5it1oVbgM-TSHgLSJoCJEZBw6fY9eG98q9xV1fu5D2kP7aDEH5weYfDca0ABOgzXKoZAt_GB-qmS8QzGN-uJBcbdXNsLD1Xe3OH375vPBu8nxyeHRwf7xpKsZTpOSUaBYlA1ntO4rgqFpcUkZZ7gH0WpS1rRpa0FL3HIsoOpBKczLilDIqWrZbvHkyndhfZSrdEZJGeFlFtQkE0dXhPbqTC6CGVS4kF4ZeRnwYSZVyMmzIFnFuGgoL9um5pTXTYdrkd-aVflgGmevV6vdxjZXrAOXgrJrput_nJnLmT-XomqauhbZ4PnKIPhvI8QkBxM7sFY58OPy3LgiDOOGZvTpLXTz7VbUTOULGNf7vG-3NJX7AleCV7gsMzXZQM1y1-RD5o7sTQ6v8dMNfH40DKbbKHixJshMgh9ppsYY5dGnj__Bfvh39uTLOvvsBjsHZdM8ejsumzKug49vVvFP-a4HKgN7V0AXfIwBetmZdNncOQ3GSoLlcnqvCyKX0ytX05vF_Jb42v-vst9c2UbY |
| CitedBy_id | crossref_primary_10_1155_2022_4947684 crossref_primary_10_1007_s11655_022_3729_y crossref_primary_10_3390_gucdd3020008 crossref_primary_10_1186_s12944_023_01806_2 crossref_primary_10_1371_journal_pone_0295038 crossref_primary_10_1016_j_joca_2021_12_001 crossref_primary_10_1038_s41598_025_13125_w crossref_primary_10_1186_s12891_024_08151_0 crossref_primary_10_1186_s13075_022_02933_4 crossref_primary_10_1038_s41416_021_01655_9 crossref_primary_10_1093_bib_bbae086 crossref_primary_10_1016_j_heliyon_2024_e31535 crossref_primary_10_1038_s41598_021_02740_y crossref_primary_10_1016_j_numecd_2022_01_022 crossref_primary_10_1093_eurjpc_zwac100 crossref_primary_10_3389_fendo_2022_835154 crossref_primary_10_1210_clinem_dgac484 crossref_primary_10_1016_j_jbspin_2020_05_002 crossref_primary_10_1038_s41467_024_47805_4 crossref_primary_10_3389_fendo_2022_917056 crossref_primary_10_1136_jmedgenet_2021_107696 crossref_primary_10_1007_s11886_022_01829_8 crossref_primary_10_1016_j_rhum_2020_07_009 crossref_primary_10_1186_s12872_024_03821_2 crossref_primary_10_1161_JAHA_121_023301 crossref_primary_10_1093_rheumatology_keaa773 crossref_primary_10_3389_fendo_2023_1195888 crossref_primary_10_1002_acr_25018 crossref_primary_10_1007_s43657_021_00033_y crossref_primary_10_1016_j_ebiom_2023_104488 crossref_primary_10_1016_j_gene_2022_146340 crossref_primary_10_1016_j_jjcc_2020_12_013 crossref_primary_10_15829_1728_8800_2025_4389 crossref_primary_10_1093_ajh_hpaa044 crossref_primary_10_1016_j_numecd_2022_03_026 crossref_primary_10_1161_HYPERTENSIONAHA_120_16547 crossref_primary_10_7554_eLife_62998 crossref_primary_10_1016_j_heliyon_2024_e24548 crossref_primary_10_1186_s12916_022_02658_w crossref_primary_10_3389_fimmu_2021_720876 crossref_primary_10_1111_liv_15564 crossref_primary_10_3389_fcvm_2025_1433107 crossref_primary_10_1136_bmjresp_2022_001535 crossref_primary_10_3389_fphar_2020_00642 crossref_primary_10_1186_s41927_024_00449_9 crossref_primary_10_1186_s12906_020_03055_7 crossref_primary_10_1097_BOR_0000000000000691 crossref_primary_10_1210_clinem_dgac192 crossref_primary_10_1177_23523735251370863 crossref_primary_10_1186_s40001_024_01920_6 crossref_primary_10_3389_fnagi_2022_822350 crossref_primary_10_1007_s10620_020_06329_9 crossref_primary_10_1016_j_ebiom_2022_103865 crossref_primary_10_1021_acssynbio_4c00831 crossref_primary_10_1038_s41392_024_01916_y crossref_primary_10_1186_s13075_023_03115_6 crossref_primary_10_1136_rmdopen_2024_004552 crossref_primary_10_3389_fcvm_2024_1481872 crossref_primary_10_1161_CIRCGEN_121_003312 crossref_primary_10_2337_dc20_0643 crossref_primary_10_1038_s10038_021_00968_0 crossref_primary_10_1111_jch_14405 crossref_primary_10_1007_s00431_023_05297_2 crossref_primary_10_1093_rheumatology_keac254 crossref_primary_10_1155_2021_2741131 crossref_primary_10_1007_s40618_021_01513_8 crossref_primary_10_1016_j_cpcardiol_2021_100798 crossref_primary_10_1371_journal_pmed_1003163 crossref_primary_10_1155_2022_2199317 crossref_primary_10_1186_s13075_020_02173_4 crossref_primary_10_2147_IJGM_S499413 crossref_primary_10_1007_s12020_024_04038_1 crossref_primary_10_1016_j_lanwpc_2025_101572 crossref_primary_10_1097_MD_0000000000040591 crossref_primary_10_1302_2046_3758_137_BJR_2023_0403_R1 crossref_primary_10_3389_fimmu_2024_1278327 crossref_primary_10_1016_j_ijmedinf_2023_105209 crossref_primary_10_1186_s40001_023_01208_1 crossref_primary_10_1038_s41598_025_88887_4 crossref_primary_10_1038_s41467_025_63395_1 crossref_primary_10_1111_jch_14792 crossref_primary_10_3389_fendo_2022_890305 crossref_primary_10_1038_s41598_023_29651_4 crossref_primary_10_1093_ije_dyac186 crossref_primary_10_1111_srt_13663 crossref_primary_10_1016_j_numecd_2020_09_012 crossref_primary_10_1016_j_jhazmat_2024_134312 crossref_primary_10_1038_s10038_020_00863_0 crossref_primary_10_1186_s12872_025_04611_0 crossref_primary_10_3389_fcell_2021_642141 crossref_primary_10_1007_s00296_022_05148_7 crossref_primary_10_1161_HYPERTENSIONAHA_122_17956 |
| Cites_doi | 10.1136/bmj.f4262 10.1155/2014/852954 10.1038/ng.106 10.1038/ng.2500 10.1038/ng.3926 10.1007/s004390051050 10.1136/annrheumdis-2017-212534 10.1016/S2213-8587(15)00386-1 10.1016/S0140-6736(08)61343-4 10.1681/ASN.2014070660 10.1101/173682 10.1371/journal.pone.0011690 10.1136/annrheumdis-2016-210602 10.1097/MOL.0000000000000155 10.1038/nbt.2749 10.1371/journal.pone.0114259 10.1001/jama.300.8.924 10.1097/BOR.0b013e32835d951e 10.1007/s11926-010-0094-1 10.1371/journal.pgen.1000504 10.1155/2015/127596 10.1136/ard.51.3.375 10.1101/078972 10.1182/blood-2012-08-449272 10.1136/bmj.j2376 10.1371/journal.pmed.1002725 10.1056/NEJMra0800885 10.1097/HJH.0000000000000701 |
| ContentType | Journal Article |
| Copyright | COPYRIGHT 2019 Public Library of Science 2019 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2019 Li et al 2019 Li et al |
| Copyright_xml | – notice: COPYRIGHT 2019 Public Library of Science – notice: 2019 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: 2019 Li et al 2019 Li et al |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM IOV ISN ISR 3V. 7TK 7X7 7XB 88E 8FI 8FJ 8FK ABUWG AFKRA AZQEC BENPR CCPQU DWQXO FYUFA GHDGH K9. M0S M1P PHGZM PHGZT PIMPY PJZUB PKEHL PPXIY PQEST PQQKQ PQUKI PRINS 7X8 5PM DOA CZK |
| DOI | 10.1371/journal.pmed.1002937 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Gale In Context: Opposing Viewpoints Gale In Context: Canada Gale In Context: Science ProQuest Central (Corporate) Neurosciences Abstracts ProQuest Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) ProQuest Hospital Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central UK/Ireland ProQuest Central Essentials ProQuest Central ProQuest One Community College ProQuest Central ProQuest Health & Medical Collection Health Research Premium Collection (Alumni) ProQuest Health & Medical Complete (Alumni) ProQuest Health & Medical Collection Medical Database Proquest Central Premium ProQuest One Academic (New) Publicly Available Content Database ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Academic (retired) ProQuest One Academic UKI Edition ProQuest Central China MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals PLoS Medicine |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Publicly Available Content Database ProQuest One Academic Middle East (New) ProQuest Central Essentials ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) ProQuest One Community College ProQuest One Health & Nursing ProQuest Central China ProQuest Central ProQuest Health & Medical Research Collection Health Research Premium Collection Health and Medicine Complete (Alumni Edition) ProQuest Central Korea Health & Medical Research Collection ProQuest Central (New) ProQuest Medical Library (Alumni) ProQuest One Academic Eastern Edition ProQuest Hospital Collection Health Research Premium Collection (Alumni) Neurosciences Abstracts ProQuest Hospital Collection (Alumni) ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition ProQuest One Academic ProQuest One Academic (New) ProQuest Central (Alumni) MEDLINE - Academic |
| DatabaseTitleList | Publicly Available Content Database MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: DOA name: Directory of Open Access Journals (DOAJ) url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: PIMPY name: Publicly Available Content Database url: http://search.proquest.com/publiccontent sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine Public Health |
| DocumentTitleAlternate | A phenome-wide mendelian randomization study on serum urate levels |
| EISSN | 1549-1676 |
| ExternalDocumentID | 2314540681 oai_doaj_org_article_373469245b9842489c08689cd370e9d0 PMC6799886 A607647055 31626644 10_1371_journal_pmed_1002937 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GeographicLocations | United Kingdom United Kingdom--UK United States--US Tennessee Nashville Tennessee |
| GeographicLocations_xml | – name: United Kingdom – name: Nashville Tennessee – name: Tennessee – name: United Kingdom--UK – name: United States--US |
| GrantInformation_xml | – fundername: Cancer Research UK grantid: 22804 – fundername: Medical Research Council grantid: MC_PC_17228 – fundername: Medical Research Council grantid: MC_QA137853 – fundername: Cancer Research UK grantid: C31250/A22804 – fundername: NHLBI NIH HHS grantid: R01 HL133786 – fundername: ; grantid: R01 HL133786 – fundername: ; grantid: C31250/A22804 |
| GroupedDBID | --- 123 29O 2WC 53G 5VS 7X7 88E 8FI 8FJ AAFWJ AAUCC AAWOE AAWTL AAYXX ABDBF ABUWG ACCTH ACGFO ACIHN ACPRK ACUHS ADBBV AEAQA AENEX AFFHD AFKRA AFPKN AFRAH AFXKF AHMBA AKRSQ ALMA_UNASSIGNED_HOLDINGS AOIJS B0M BAIFH BAWUL BBTPI BCNDV BENPR BPHCQ BVXVI BWKFM CCPQU CITATION CS3 DIK DU5 E3Z EAP EAS EBD EBS EJD EMK EMOBN ESX F5P FPL FYUFA GROUPED_DOAJ GX1 HMCUK HYE IAO IHR IHW INH INR IOF IOV IPO ISN ISR ITC KQ8 M1P M48 MK0 O5R O5S OK1 OVT P2P PHGZM PHGZT PIMPY PJZUB PPXIY PQQKQ PROAC PSQYO PV9 RNS RPM RZL SV3 TR2 TUS UKHRP WOW XSB YZZ ~8M ADRAZ ADXHL ALIPV CGR CUY CVF ECM EIF H13 IPNFZ NPM RIG WOQ 3V. 7TK 7XB 8FK AZQEC DWQXO K9. PKEHL PQEST PQUKI PRINS 7X8 PUEGO 5PM AAPBV ABPTK BCGST CZK ICW M~E N95 |
| ID | FETCH-LOGICAL-c830t-532e206594328f710e9b0523430fe6bd15829b86250b406e7feaa045712e937b3 |
| IEDL.DBID | FPL |
| ISICitedReferencesCount | 99 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000495435800022&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1549-1676 1549-1277 |
| IngestDate | Sun Jun 04 13:13:08 EDT 2023 Fri Oct 03 12:51:14 EDT 2025 Tue Nov 04 01:55:05 EST 2025 Thu Oct 02 11:10:23 EDT 2025 Sat Nov 29 14:46:38 EST 2025 Tue Nov 11 10:34:26 EST 2025 Sat Nov 29 11:23:33 EST 2025 Tue Nov 04 18:06:22 EST 2025 Thu Nov 13 15:23:27 EST 2025 Thu Nov 13 14:25:54 EST 2025 Thu Nov 13 15:17:29 EST 2025 Thu May 22 21:08:31 EDT 2025 Mon Jul 21 05:42:55 EDT 2025 Sat Nov 29 05:16:38 EST 2025 Tue Nov 18 22:19:01 EST 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 10 |
| Language | English |
| License | This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Creative Commons Attribution License |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c830t-532e206594328f710e9b0523430fe6bd15829b86250b406e7feaa045712e937b3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 The authors have declared that no competing interests exist. |
| ORCID | 0000-0002-6169-6262 0000-0002-3049-7332 0000-0002-5929-6585 0000-0002-2503-4253 0000-0002-2939-1055 0000-0001-6880-2577 0000-0003-4889-4640 0000-0002-4275-9328 0000-0001-5887-9132 |
| OpenAccessLink | http://dx.doi.org/10.1371/journal.pmed.1002937 |
| PMID | 31626644 |
| PQID | 2314540681 |
| PQPubID | 1436338 |
| ParticipantIDs | plos_journals_2314540681 doaj_primary_oai_doaj_org_article_373469245b9842489c08689cd370e9d0 pubmedcentral_primary_oai_pubmedcentral_nih_gov_6799886 proquest_miscellaneous_2307130092 proquest_journals_2314540681 gale_infotracmisc_A607647055 gale_infotracgeneralonefile_A607647055 gale_infotracacademiconefile_A607647055 gale_incontextgauss_ISR_A607647055 gale_incontextgauss_ISN_A607647055 gale_incontextgauss_IOV_A607647055 gale_healthsolutions_A607647055 pubmed_primary_31626644 crossref_citationtrail_10_1371_journal_pmed_1002937 crossref_primary_10_1371_journal_pmed_1002937 |
| PublicationCentury | 2000 |
| PublicationDate | 20191018 |
| PublicationDateYYYYMMDD | 2019-10-18 |
| PublicationDate_xml | – month: 10 year: 2019 text: 20191018 day: 18 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: San Francisco – name: San Francisco, CA USA |
| PublicationTitle | PLoS medicine |
| PublicationTitleAlternate | PLoS Med |
| PublicationYear | 2019 |
| Publisher | Public Library of Science Public Library of Science (PLoS) |
| Publisher_xml | – name: Public Library of Science – name: Public Library of Science (PLoS) |
| References | M Kolz (pmed.1002937.ref007) 2009; 5 C Li (pmed.1002937.ref025) 2013; 25 A Dehghan (pmed.1002937.ref009) 2008; 372 ME Kleber (pmed.1002937.ref013) 2015; 26 X Li (pmed.1002937.ref015) 2018; 77 M Bi (pmed.1002937.ref027) 2010; 5 pmed.1002937.ref020 L Billiet (pmed.1002937.ref023) 2014; 2014 B Combe (pmed.1002937.ref029) 2017; 76 V Vitart (pmed.1002937.ref010) 2008; 40 JC Denny (pmed.1002937.ref017) 2013; 31 A Raimondo (pmed.1002937.ref026) 2015; 26 J White (pmed.1002937.ref011) 2016; 4 DM Jordan (pmed.1002937.ref014) 2019; 16 J Wang (pmed.1002937.ref022) 2014; 9 M Mazzali (pmed.1002937.ref004) 2010; 12 pmed.1002937.ref019 A Kottgen (pmed.1002937.ref008) 2013; 45 A Mazharian (pmed.1002937.ref028) 2013; 121 TM Palmer (pmed.1002937.ref012) 2013; 347 BT Emmerson (pmed.1002937.ref005) 1992; 51 A Cortes (pmed.1002937.ref016) 2017; 49 DI Feig (pmed.1002937.ref021) 2008; 300 JB Wilk (pmed.1002937.ref006) 2000; 106 HY Benjamini Yoav (pmed.1002937.ref018) 1995; 72 X Li (pmed.1002937.ref001) 2017; 357 DI Feig (pmed.1002937.ref002) 2008; 359 C Borghi (pmed.1002937.ref003) 2015; 33 TC Peng (pmed.1002937.ref024) 2015; 2015 |
| References_xml | – volume: 347 start-page: f4262 year: 2013 ident: pmed.1002937.ref012 article-title: Association of plasma uric acid with ischaemic heart disease and blood pressure: mendelian randomisation analysis of two large cohorts publication-title: BMJ doi: 10.1136/bmj.f4262 – volume: 2014 start-page: 1 year: 2014 ident: pmed.1002937.ref023 article-title: Review of hyperuricemia as new marker for metabolic syndrome publication-title: ISRN Rheumatol doi: 10.1155/2014/852954 – volume: 40 start-page: 437 issue: 4 year: 2008 ident: pmed.1002937.ref010 article-title: SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout publication-title: Nat Genet doi: 10.1038/ng.106 – volume: 45 start-page: 145 issue: 2 year: 2013 ident: pmed.1002937.ref008 article-title: Genome-wide association analyses identify 18 new loci associated with serum urate concentrations publication-title: Nat Genet doi: 10.1038/ng.2500 – volume: 72 start-page: 405 issue: 4 year: 1995 ident: pmed.1002937.ref018 article-title: Controlling the false discovery rate: a practical and powerful approach to multiple testing publication-title: J R Stat Soc – volume: 49 start-page: 1311 issue: 9 year: 2017 ident: pmed.1002937.ref016 article-title: Bayesian analysis of genetic association across tree-structured routine healthcare data in the UK Biobank publication-title: Nat Genet doi: 10.1038/ng.3926 – volume: 106 start-page: 355 issue: 3 year: 2000 ident: pmed.1002937.ref006 article-title: Segregation analysis of serum uric acid in the NHLBI Family Heart Study publication-title: Hum Genet doi: 10.1007/s004390051050 – volume: 77 start-page: 1039 issue: 7 year: 2018 ident: pmed.1002937.ref015 article-title: MR-PheWAS: exploring the causal effect of SUA level on multiple disease outcomes by using genetic instruments in UK Biobank publication-title: Ann Rheum Dis doi: 10.1136/annrheumdis-2017-212534 – volume: 4 start-page: 327 issue: 4 year: 2016 ident: pmed.1002937.ref011 article-title: Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis publication-title: Lancet Diabetes Endocrinol doi: 10.1016/S2213-8587(15)00386-1 – volume: 372 start-page: 1953 issue: 9654 year: 2008 ident: pmed.1002937.ref009 article-title: Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study publication-title: Lancet doi: 10.1016/S0140-6736(08)61343-4 – volume: 26 start-page: 2831 issue: 11 year: 2015 ident: pmed.1002937.ref013 article-title: Uric Acid and Cardiovascular Events: A Mendelian Randomization Study publication-title: J Am Soc Nephrol doi: 10.1681/ASN.2014070660 – ident: pmed.1002937.ref020 doi: 10.1101/173682 – volume: 5 start-page: e11690 issue: 7 year: 2010 ident: pmed.1002937.ref027 article-title: Association of rs780094 in GCKR with metabolic traits and incident diabetes and cardiovascular disease: the ARIC Study publication-title: PLoS ONE doi: 10.1371/journal.pone.0011690 – volume: 76 start-page: 948 issue: 6 year: 2017 ident: pmed.1002937.ref029 article-title: 2016 update of the EULAR recommendations for the management of early arthritis publication-title: Ann Rheum Dis doi: 10.1136/annrheumdis-2016-210602 – volume: 26 start-page: 88 issue: 2 year: 2015 ident: pmed.1002937.ref026 article-title: Glucokinase regulatory protein: complexity at the crossroads of triglyceride and glucose metabolism publication-title: Curr Opin Lipidol doi: 10.1097/MOL.0000000000000155 – volume: 31 start-page: 1102 issue: 12 year: 2013 ident: pmed.1002937.ref017 article-title: Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data publication-title: Nat Biotechnol doi: 10.1038/nbt.2749 – volume: 9 start-page: e114259 issue: 12 year: 2014 ident: pmed.1002937.ref022 article-title: Hyperuricemia and risk of incident hypertension: a systematic review and meta-analysis of observational studies publication-title: PLoS ONE doi: 10.1371/journal.pone.0114259 – volume: 300 start-page: 924 year: 2008 ident: pmed.1002937.ref021 article-title: Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial publication-title: JAMA doi: 10.1001/jama.300.8.924 – volume: 25 start-page: 210 issue: 2 year: 2013 ident: pmed.1002937.ref025 article-title: Metabolic syndrome, diabetes, and hyperuricemia publication-title: Curr Opin Rheumatol doi: 10.1097/BOR.0b013e32835d951e – volume: 12 start-page: 108 issue: 2 year: 2010 ident: pmed.1002937.ref004 article-title: Uric acid and hypertension: cause or effect? publication-title: Curr Rheumatol Rep doi: 10.1007/s11926-010-0094-1 – volume: 5 start-page: e1000504 issue: 6 year: 2009 ident: pmed.1002937.ref007 article-title: Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations publication-title: PLoS Genet doi: 10.1371/journal.pgen.1000504 – volume: 2015 start-page: 1 year: 2015 ident: pmed.1002937.ref024 article-title: Relationship between hyperuricemia and lipid profiles in US adults publication-title: Biomed Res Int doi: 10.1155/2015/127596 – volume: 51 start-page: 375 issue: 3 year: 1992 ident: pmed.1002937.ref005 article-title: Genetic control of the renal clearance of urate: a study of twins publication-title: Ann Rheum Dis doi: 10.1136/ard.51.3.375 – ident: pmed.1002937.ref019 doi: 10.1101/078972 – volume: 121 start-page: 4205 issue: 20 year: 2013 ident: pmed.1002937.ref028 article-title: Megakaryocyte-specific deletion of the protein-tyrosine phosphatases Shp1 and Shp2 causes abnormal megakaryocyte development, platelet production, and function publication-title: Blood doi: 10.1182/blood-2012-08-449272 – volume: 357 start-page: j2376 year: 2017 ident: pmed.1002937.ref001 article-title: Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies publication-title: BMJ doi: 10.1136/bmj.j2376 – volume: 16 start-page: e1002725 issue: 1 year: 2019 ident: pmed.1002937.ref014 article-title: No causal effects of serum urate levels on the risk of chronic kidney disease: A Mendelian randomization study publication-title: PLoS Med doi: 10.1371/journal.pmed.1002725 – volume: 359 start-page: 1811 issue: 17 year: 2008 ident: pmed.1002937.ref002 article-title: Uric Acid and Cardiovascular Risk publication-title: N Engl J Med doi: 10.1056/NEJMra0800885 – volume: 33 start-page: 1729 issue: 9 year: 2015 ident: pmed.1002937.ref003 article-title: Serum uric acid and the risk of cardiovascular and renal disease publication-title: J Hypertens doi: 10.1097/HJH.0000000000000701 |
| SSID | ssj0029090 |
| Score | 2.6038969 |
| Snippet | The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect... Background The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal... Evropi Theodoratou and colleagues investigate possible mechanisms linking urate with cardiovascular disease. BackgroundThe role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal... Background The role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal... |
| SourceID | plos doaj pubmedcentral proquest gale pubmed crossref |
| SourceType | Open Website Open Access Repository Aggregation Database Index Database Enrichment Source |
| StartPage | e1002937 |
| SubjectTerms | Adult Aged Analysis Angina Angina pectoris Arteriosclerosis Arthritis Atherosclerosis Bayes Theorem Bayesian analysis Biological Specimen Banks Biology and Life Sciences Cardiovascular diseases Cardiovascular Diseases - blood Cardiovascular Diseases - complications Cardiovascular Diseases - genetics Cerebral infarction Cerebrovascular diseases Cohort Studies Comorbidity Coronary artery disease Coronary heart disease Diabetes Drug delivery Epidemiology Female Genetic analysis Genetic diversity Genetic Pleiotropy Genetic Predisposition to Disease Genetic variance Genetic Variation Genetics Genome-wide association studies Genome-Wide Association Study Genomes Genomics Gout Health sciences Heart attack Heart diseases Heart failure Humans Hypercholesterolemia Hypertension Informatics Ischemia Male Medical research Medicine and Health Sciences Mendelian Randomization Analysis Metabolic disorders Metabolic syndrome Middle Aged Myocardial infarction Myocardial ischemia Phenomics Phenotype Phenotypes Pleiotropy Polymorphism, Single Nucleotide Public health Randomization Reproducibility of Results Sensitivity and Specificity Social Sciences Software Studies Supervision Systematic review Treatment Outcome Type 2 diabetes United Kingdom Uric acid Uric Acid - blood Vascular diseases |
| SummonAdditionalLinks | – databaseName: DOAJ Directory of Open Access Journals dbid: DOA link: http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Nj9MwELVQhRAXxPcGFjAIwSlsEjuxza2LWIGAgoBd7S2KY2e3ok2qpgXxN_jFzDhu1KBKuwcuOdgvkTIztmfG42dCngtTRpXELX-mTciNjkNtCxUag9bARRo7Up-Tj2Iykaen6svWVV9YE9bRA3eCO2CCQQSX8FQryRMuVQlOODwNE5FVxkXr4PVsgikfaqnIZVeQfyyMEyH8oTkm4gOvo1cLWG0cAanCO9C3FiXH3d_P0KPFrGl3uZ__VlFuLUtHN8kN70_Scfcft8gVW98m1z75HfM75A_ySrt89ew3Nb72xRoKlree0zUSRdAZFg61tKgNLQflqa7JHdGifiOnpdOaHn-gh1OYB-ofFO_XXa5e0zHFWrFmbsNfU2PpHBPrmEChsBSaZu4Pe1JHZnuXHB-9_f7mXejvYQhLyaJVmLLEJrj_ylkiK3BJrNKYTeYsqmymTZzKRGkIjdJIg39gRWWLAlxFEScWhKvZPTKqm9ruEWqgCQKYTJcQx8Q8LaySWvMK_CRjeWQDwjaKyEtPUo53Zcxyt_MmIFjp5Jqj-nKvvoCE_VuLjqTjAvwh6rjHIsW2awDDy73h5RcZXkCeoIXk3XnVfqLIx1kkMo4kRQF55hBIs1FjHc9ZsW7b_P3nk0uAvk0uA_o6AL30oKoBmZWFP2ABkkeOrwHyxQB51jGc7wLuD4Aw9ZSD7j0cHRsZtzkEC8jomMkY3tyMmN3dT_tu_ChW-tW2WSMG8yZIBRaQ-90A6_XEYgi_wYEPiBgMvYEihz319NxxpmdCKSmzB_9D8w_JdXCbFXowsdwno9VybR-Rq-XP1bRdPnYT0V84bInN priority: 102 providerName: Directory of Open Access Journals – databaseName: ProQuest Central dbid: BENPR link: http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3db9MwELegQwgJ8TE-FhhgEGJPYUmcxjYvqEWbQECZBpv2FsWxUyrapDQtiH-Dv5g7xw0LmmASL32IL1V7Pp_v83eEPOU6DwqBKX-mtB9rFfrKZNLXGqUh5v3Qgvocv-OjkTg5kQcu4Fa7ssq1TrSKWlc5xsh3wQ5BsLhEhC_nX32cGoXZVTdC4yLZQKSyuEc2hnujg8PW5ZKBjbIgDpkfRpy75jnGw123V8_ncOtYIFKJs9BPXU4Ww7_V1L35tKrPMkP_rKY8dT3tX__fP3aDXHOGKR00knSTXDDlJrn83qXeN8nVJsBHm76lW-QnAlbbQPj0B9WuqMZoCiK9mtEVIlDQKVYk1TQrNc07da_2ke39oi5DVNNJSY_e0uEEFEz5heLg3sXyBR1QLEKrZsb_PtGGzjBij5EZCnesrmaui5RalNzb5Gh_79Or174b8ODnggVLv88iE2FiN2aRKMDWMVJhmDpmQWESpcO-iKQCn6sfKOCQ4YXJMrBBeRgZ2C3F7pBeWZVmi1ANj8AzSlQODhIwNDNSKBUXYIBpEwfGI2y9s2nu0M9xCMc0tSk9Dl5Qw-cU5SF18uARv31r3qB__IN-iELT0iJ2t31QLcapUwUp4yxOwO3tKyniKBYyB7cSPjXjwAAdeOQRilzaNMK2GigdJAFPYkQ_8sgTS4H4HSUWCI2zVV2nbz4cn4Po4-g8RIcdoh1HVFTAszxznRvAeQQP61A-61COG-j0swi3O4Sg0_LO8hYetzWP6_T3IYE318fo7OXH7TJ-KZYQlqZaIQ0GZBBjzCN3mxPb7hMLwa8Hz8AjvHOWOxvZXSknny0Ye8KlFCK59_efdZ9cAUtbotETim3SWy5W5gG5lH9bTurFQ6e1fgGqRaAC priority: 102 providerName: ProQuest |
| Title | Genetically determined serum urate levels and cardiovascular and other diseases in UK Biobank cohort: A phenome-wide mendelian randomization study |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/31626644 https://www.proquest.com/docview/2314540681 https://www.proquest.com/docview/2307130092 https://pubmed.ncbi.nlm.nih.gov/PMC6799886 https://doaj.org/article/373469245b9842489c08689cd370e9d0 http://dx.doi.org/10.1371/journal.pmed.1002937 |
| Volume | 16 |
| WOSCitedRecordID | wos000495435800022&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVAON databaseName: Directory of Open Access Journals (DOAJ) customDbUrl: eissn: 1549-1676 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0029090 issn: 1549-1676 databaseCode: DOA dateStart: 20040101 isFulltext: true titleUrlDefault: https://www.doaj.org/ providerName: Directory of Open Access Journals – providerCode: PRVPQU databaseName: Health & Medical Collection customDbUrl: eissn: 1549-1676 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0029090 issn: 1549-1676 databaseCode: 7X7 dateStart: 20041001 isFulltext: true titleUrlDefault: https://search.proquest.com/healthcomplete providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Central customDbUrl: eissn: 1549-1676 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0029090 issn: 1549-1676 databaseCode: BENPR dateStart: 20041001 isFulltext: true titleUrlDefault: https://www.proquest.com/central providerName: ProQuest – providerCode: PRVPQU databaseName: Publicly Available Content Database customDbUrl: eissn: 1549-1676 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0029090 issn: 1549-1676 databaseCode: PIMPY dateStart: 20041001 isFulltext: true titleUrlDefault: http://search.proquest.com/publiccontent providerName: ProQuest – providerCode: PRVATS databaseName: Public Library of Science (PLoS) Journals Open Access customDbUrl: eissn: 1549-1676 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0029090 issn: 1549-1676 databaseCode: FPL dateStart: 20040101 isFulltext: true titleUrlDefault: http://www.plos.org/publications/ providerName: Public Library of Science |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwlV1bb9MwFLZYhxAS4jIuC4xiEGJPgSROYoe3Fq1iYivVYFN5ipLYGRVtUjUtiL_BL-Ycxw1k6sR4yYP9JYqOb-f6mZCXXGZOLjDkz1Jp-zJ17VQlkS0lzgafB64m9Tk74sOhGI-j0R9D8UIEn3H3jZHp6zmcDpowFA7ULbLtsTDEFK7B6KgxsCInckx53GVvto4fzdLf7MWd-bSsNimaF_Ml_zqABnf-99fvkttG1aS9em7cI9dUsUNuHJtg-g65VbvsaF2JdJ_8Qgpq7dqe_qTSpMkoSWGSrmZ0hZwSdIo5RhVNCkmzViarbtLVXNTEfCo6KejpB9qfwJZRfKN4Fe9i-Zb2KKaVlTNl_5hIRWfog0dfC4VTU5YzUxdKNe_tA3I6OPj87r1trmywM8GcpR0wT3kYqvWZJ3LQXlSUouPZZ06uwlS6gfCiFKyowElBlVA8V0kCWiV3PQXCSdlD0inKQu0SKqEJbJ0wzcDkcf0gUZFIUz8HlUoq31EWYeuRjDPDZ47XakxjHaTjYNfUco5R_LERv0Xs5q15zefxD3wfJ0mDRTZu3QDjHJvFHTPO_BAM2SCNhO_5IsrAUISnZBwEIB2LPMMpFtelrc2eEvdCh4c-8hlZ5IVGICNHgSk_58mqquLDj2dXAH0aXgV00gLtG1BegsyyxNRigOSRDqyFfNVCntdk6JuAey0g7FJZq3sXl9daxlUMdgWSP4bChTfXS25z9_OmGz-KSYGFKleIQRcLsoZZ5FG9QptxYi5Y6qDrW4S31m5rINs9xeSrplcPeRQJET6-_I-fkJugN0eowrhij3SWi5V6Sq5n35eTatElW3zM9VN0yXb_YDg66WpXT1fvVtA2OjweffkNiPSRJw |
| linkProvider | Public Library of Science |
| linkToHtml | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V3db9MwELdGQYCE-BgfCwxmEB9PYUmcxgkSQh0wrepWEGxT30ISO6WiTUrTMu3f4A_hb-TOcbIFVbCXPfDSB_uSRufz-e589ztCnnKRWKmPV_4sFqYrYtuMZRSYQqA0uLxtK1Cfw13e7_uDQfBxhfyqamEwrbLSiUpRizzBGPkm2CEIFuf59pvpdxO7RuHtatVCoxSLnjw-ApeteN19B-v7zHG23--_3TF1VwEz8Zk1N9vMkQ7eJrrM8VM4YGUQY2zUZVYqvVjYbd8JYjD021YM_yd5KqMIDB9uOxLO8pjBey-Qi6DHOaaQ8cGJgxdYKqaDqGem7XCuS_UYtze1ZLycwhmnYE8D7Lx-6ihUHQPqc6E1HefFMqP3z9zNU4fh9o3_jY03yXVtdtNOuU9ukRWZrZLLezqxYJVcK8OXtKzKuk1-Ihy3CvOPj6nQKUNSUNiwiwldIL4GHWO-VUGjTNCkkdWrhlRlG9X3XwUdZfSgR7dGoD6zbxTbEs_mr2iHYopdPpHm0UhIOsH7CIw7UbAgRD7RNbJUYQDfIQfnwqG7pJXlmVwjVMAQ-H1enID7BwsYycCPYzcF81JI15IGYZUkhYnGdscWI-NQXVhy8PFKPocof6GWP4OY9VPTEtvkH_RbKKQ1LSKTq4F8Ngy1ogsZZ64HTn07DnzXcf0gAacZfgXjwABhGWQDRTwsy3xr_Rp2PIt7LmI7GeSJokB0kgzTn4bRoijC7ofDMxB97p-F6FOD6IUmSnPgWRLpuhTgPEKjNSifNyiHJTD8MsL1BiFo7KQxvYbbu-JxEZ5sSniy2rbLpx_X0_hSTJDMZL5AGgw3IYKaQe6VGqJeJ2Z7YIa7rkF4Q3c0FrI5k42-Kqh5jweB73v3__5ZG-TKzv7ebrjb7fcekKvgUwRo3tn-OmnNZwv5kFxKfsxHxeyR0peUfDlvzfIb7fH3Og |
| linkToPdf | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMw1V1Lb9NAEF6VFFVIiEd51FDognicTPzYeG0khFJKRNQ2RIVW5WRs7zpEJHaIE6r-DX4Ov46Z9cbUKIJeeuCSw-7YsWZnZ2d2Zr4h5AkXiZX6GPJ3Y2EyEdtmLKPAFAKlgfGWrUB9jvZ4r-cfHwf9FfJzUQuDaZULnagUtcgTvCNvgh2CYHGebzdTnRbR3-m8nnwzsYMURloX7TRKEdmVpyfgvhWvujuw1k8dp_P245t3pu4wYCa-a83MlutIByOLzHX8FA5bGcR4T8pcK5VeLOyW7wQxGP0tK4b_ljyVUQRGELcdCed67MJ7L5FVMMkZ7LHVfne__6ly9wJL3fAgBpppO5zrwj2X200tJy8mcOIpENQA-7CfORhV_4DqlGhMRnmxzAT-M5PzzNHYuf4_M_UGuaYNctoud9BNsiKzdbK2r1MO1snV8mKTlvVat8gPBOpWAYDRKRU6mUgKClt5PqZzRN6gI8zEKmiUCZrU8n3VkKp5ozoyVtBhRg936fYQFGv2lWLD4unsJW1TTL7Lx9I8GQpJxxipwBspCraFyMe6epYqdODb5PBCOHSHNLI8kxuEChgC8fPiBBxDWMxIBn4csxQMTyGZJQ3iLqQqTDTqOzYfGYUqlMnB-yv5HKIshloWDWJWT01K1JN_0G-jwFa0iFmuBvLpINQqMHS5yzxw91tx4DOH-UEC7jT8CpcDA4RlkC0U97AsAK40b9j2LO4xRH0yyGNFgbglGQrrIJoXRdh9f3QOog-98xAd1Iiea6I0B54lka5YAc4jaFqN8lmNclBCxi8j3KwRgi5PatMbuNUXPC7C3xsUnlxs4eXTj6ppfCmmTmYynyMNXkQhtppB7pbaolon1_bAQGfMILymR2oLWZ_Jhl8UCL3Hg8D3vXt__6wtsgYKJdzr9nbvkyvgbARo99n-JmnMpnP5gFxOvs-GxfShVp6UfL5o1fILOtYBmA |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Genetically+determined+serum+urate+levels+and+cardiovascular+and+other+diseases+in+UK+Biobank+cohort%3A+A+phenome-wide+mendelian+randomization+study&rft.jtitle=PLoS+medicine&rft.au=Li%2C+Xue&rft.au=Meng%2C+Xiangrui&rft.au=He%2C+Yazhou&rft.au=Spiliopoulou%2C+Athina&rft.date=2019-10-18&rft.pub=Public+Library+of+Science&rft.issn=1549-1277&rft.volume=16&rft.issue=10&rft_id=info:doi/10.1371%2Fjournal.pmed.1002937&rft.externalDocID=A607647055 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1549-1676&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1549-1676&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1549-1676&client=summon |