Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study
Background The aim of this study was to assess the associations of modifiable lifestyle factors (smoking, coffee consumption, sleep, and physical activity) and cardiometabolic factors (body mass index, glycemic traits, type 2 diabetes, systolic and diastolic blood pressure, lipids, and inflammation...
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| Published in: | Journal of the American Heart Association Vol. 10; no. 22; p. e022277 |
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| Main Authors: | , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
John Wiley and Sons Inc
16.11.2021
Wiley |
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| ISSN: | 2047-9980, 2047-9980 |
| Online Access: | Get full text |
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| Abstract | Background The aim of this study was to assess the associations of modifiable lifestyle factors (smoking, coffee consumption, sleep, and physical activity) and cardiometabolic factors (body mass index, glycemic traits, type 2 diabetes, systolic and diastolic blood pressure, lipids, and inflammation and kidney function markers) with risks of any (ruptured or unruptured) intracranial aneurysm and aneurysmal subarachnoid hemorrhage using Mendelian randomization. Methods and Results Summary statistical data for the genetic associations with the modifiable risk factors and the outcomes were obtained from meta-analyses of genome-wide association studies. The inverse-variance weighted method was used as the main Mendelian randomization analysis, with additional sensitivity analyses conducted using methods more robust to horizontal pleiotropy. Genetic predisposition to smoking, insomnia, and higher blood pressure was associated with an increased risk of both intracranial aneurysm and aneurysmal subarachnoid hemorrhage. For intracranial aneurysm, the odds ratios were 3.20 (95% CI, 1.93-5.29) per SD increase in smoking index, 1.24 (95% CI, 1.10-1.40) per unit increase in log-odds of insomnia, and 2.92 (95% CI, 2.49-3.43) per 10 mm Hg increase in diastolic blood pressure. In addition, there was weak evidence for associations of genetically predicted decreased physical activity, higher triglyceride levels, higher body mass index, and lower low-density lipoprotein cholesterol levels with higher risk of intracranial aneurysm and aneurysmal subarachnoid hemorrhage, with 95% CI overlapping the null for at least 1 of the outcomes. All results were consistent in sensitivity analyses. Conclusions This Mendelian randomization study suggests that smoking, insomnia, and high blood pressure are major risk factors for intracranial aneurysm and aneurysmal subarachnoid hemorrhage. |
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| AbstractList | Background
The aim of this study was to assess the associations of modifiable lifestyle factors (smoking, coffee consumption, sleep, and physical activity) and cardiometabolic factors (body mass index, glycemic traits, type 2 diabetes, systolic and diastolic blood pressure, lipids, and inflammation and kidney function markers) with risks of any (ruptured or unruptured) intracranial aneurysm and aneurysmal subarachnoid hemorrhage using Mendelian randomization.
Methods and Results
Summary statistical data for the genetic associations with the modifiable risk factors and the outcomes were obtained from meta‐analyses of genome‐wide association studies. The inverse‐variance weighted method was used as the main Mendelian randomization analysis, with additional sensitivity analyses conducted using methods more robust to horizontal pleiotropy. Genetic predisposition to smoking, insomnia, and higher blood pressure was associated with an increased risk of both intracranial aneurysm and aneurysmal subarachnoid hemorrhage. For intracranial aneurysm, the odds ratios were 3.20 (95% CI, 1.93–5.29) per SD increase in smoking index, 1.24 (95% CI, 1.10–1.40) per unit increase in log‐odds of insomnia, and 2.92 (95% CI, 2.49–3.43) per 10 mm Hg increase in diastolic blood pressure. In addition, there was weak evidence for associations of genetically predicted decreased physical activity, higher triglyceride levels, higher body mass index, and lower low‐density lipoprotein cholesterol levels with higher risk of intracranial aneurysm and aneurysmal subarachnoid hemorrhage, with 95% CI overlapping the null for at least 1 of the outcomes. All results were consistent in sensitivity analyses.
Conclusions
This Mendelian randomization study suggests that smoking, insomnia, and high blood pressure are major risk factors for intracranial aneurysm and aneurysmal subarachnoid hemorrhage. Background The aim of this study was to assess the associations of modifiable lifestyle factors (smoking, coffee consumption, sleep, and physical activity) and cardiometabolic factors (body mass index, glycemic traits, type 2 diabetes, systolic and diastolic blood pressure, lipids, and inflammation and kidney function markers) with risks of any (ruptured or unruptured) intracranial aneurysm and aneurysmal subarachnoid hemorrhage using Mendelian randomization. Methods and Results Summary statistical data for the genetic associations with the modifiable risk factors and the outcomes were obtained from meta-analyses of genome-wide association studies. The inverse-variance weighted method was used as the main Mendelian randomization analysis, with additional sensitivity analyses conducted using methods more robust to horizontal pleiotropy. Genetic predisposition to smoking, insomnia, and higher blood pressure was associated with an increased risk of both intracranial aneurysm and aneurysmal subarachnoid hemorrhage. For intracranial aneurysm, the odds ratios were 3.20 (95% CI, 1.93-5.29) per SD increase in smoking index, 1.24 (95% CI, 1.10-1.40) per unit increase in log-odds of insomnia, and 2.92 (95% CI, 2.49-3.43) per 10 mm Hg increase in diastolic blood pressure. In addition, there was weak evidence for associations of genetically predicted decreased physical activity, higher triglyceride levels, higher body mass index, and lower low-density lipoprotein cholesterol levels with higher risk of intracranial aneurysm and aneurysmal subarachnoid hemorrhage, with 95% CI overlapping the null for at least 1 of the outcomes. All results were consistent in sensitivity analyses. Conclusions This Mendelian randomization study suggests that smoking, insomnia, and high blood pressure are major risk factors for intracranial aneurysm and aneurysmal subarachnoid hemorrhage. Background The aim of this study was to assess the associations of modifiable lifestyle factors (smoking, coffee consumption, sleep, and physical activity) and cardiometabolic factors (body mass index, glycemic traits, type 2 diabetes, systolic and diastolic blood pressure, lipids, and inflammation and kidney function markers) with risks of any (ruptured or unruptured) intracranial aneurysm and aneurysmal subarachnoid hemorrhage using Mendelian randomization. Methods and Results Summary statistical data for the genetic associations with the modifiable risk factors and the outcomes were obtained from meta-analyses of genome-wide association studies. The inverse-variance weighted method was used as the main Mendelian randomization analysis, with additional sensitivity analyses conducted using methods more robust to horizontal pleiotropy. Genetic predisposition to smoking, insomnia, and higher blood pressure was associated with an increased risk of both intracranial aneurysm and aneurysmal subarachnoid hemorrhage. For intracranial aneurysm, the odds ratios were 3.20 (95% CI, 1.93-5.29) per SD increase in smoking index, 1.24 (95% CI, 1.10-1.40) per unit increase in log-odds of insomnia, and 2.92 (95% CI, 2.49-3.43) per 10 mm Hg increase in diastolic blood pressure. In addition, there was weak evidence for associations of genetically predicted decreased physical activity, higher triglyceride levels, higher body mass index, and lower low-density lipoprotein cholesterol levels with higher risk of intracranial aneurysm and aneurysmal subarachnoid hemorrhage, with 95% CI overlapping the null for at least 1 of the outcomes. All results were consistent in sensitivity analyses. Conclusions This Mendelian randomization study suggests that smoking, insomnia, and high blood pressure are major risk factors for intracranial aneurysm and aneurysmal subarachnoid hemorrhage.Background The aim of this study was to assess the associations of modifiable lifestyle factors (smoking, coffee consumption, sleep, and physical activity) and cardiometabolic factors (body mass index, glycemic traits, type 2 diabetes, systolic and diastolic blood pressure, lipids, and inflammation and kidney function markers) with risks of any (ruptured or unruptured) intracranial aneurysm and aneurysmal subarachnoid hemorrhage using Mendelian randomization. Methods and Results Summary statistical data for the genetic associations with the modifiable risk factors and the outcomes were obtained from meta-analyses of genome-wide association studies. The inverse-variance weighted method was used as the main Mendelian randomization analysis, with additional sensitivity analyses conducted using methods more robust to horizontal pleiotropy. Genetic predisposition to smoking, insomnia, and higher blood pressure was associated with an increased risk of both intracranial aneurysm and aneurysmal subarachnoid hemorrhage. For intracranial aneurysm, the odds ratios were 3.20 (95% CI, 1.93-5.29) per SD increase in smoking index, 1.24 (95% CI, 1.10-1.40) per unit increase in log-odds of insomnia, and 2.92 (95% CI, 2.49-3.43) per 10 mm Hg increase in diastolic blood pressure. In addition, there was weak evidence for associations of genetically predicted decreased physical activity, higher triglyceride levels, higher body mass index, and lower low-density lipoprotein cholesterol levels with higher risk of intracranial aneurysm and aneurysmal subarachnoid hemorrhage, with 95% CI overlapping the null for at least 1 of the outcomes. All results were consistent in sensitivity analyses. Conclusions This Mendelian randomization study suggests that smoking, insomnia, and high blood pressure are major risk factors for intracranial aneurysm and aneurysmal subarachnoid hemorrhage. |
| Author | Gill, Dipender Ruigrok, Ynte M. Karhunen, Ville Bakker, Mark K. Larsson, Susanna C. |
| AuthorAffiliation | 2 Research Unit of Mathematical Sciences University of Oulu Finland 8 Unit of Medical Epidemiology Department of Surgical Sciences Uppsala University Uppsala Sweden 5 Clinical Pharmacology and Therapeutics Section Institute of Medical and Biomedical Education and Institute for Infection and Immunity St George’s, University of London London United Kingdom 6 Clinical Pharmacology Group, Pharmacy and Medicines Directorate St George’s University Hospitals NHS Foundation Trust London United Kingdom 7 Novo Nordisk Research Centre Oxford Oxford United Kingdom 9 Unit of Cardiovascular and Nutritional Epidemiology Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden 3 Center for Life Course Health Research University of Oulu Finland 1 Department of Epidemiology and Biostatistics School of Public Health Imperial College London London United Kingdom 4 Department of Neurology and Neurosurgery University Medical Center Utrecht Brain Center Utrecht University Utrecht the Netherlands |
| AuthorAffiliation_xml | – name: 5 Clinical Pharmacology and Therapeutics Section Institute of Medical and Biomedical Education and Institute for Infection and Immunity St George’s, University of London London United Kingdom – name: 8 Unit of Medical Epidemiology Department of Surgical Sciences Uppsala University Uppsala Sweden – name: 7 Novo Nordisk Research Centre Oxford Oxford United Kingdom – name: 2 Research Unit of Mathematical Sciences University of Oulu Finland – name: 1 Department of Epidemiology and Biostatistics School of Public Health Imperial College London London United Kingdom – name: 9 Unit of Cardiovascular and Nutritional Epidemiology Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden – name: 3 Center for Life Course Health Research University of Oulu Finland – name: 6 Clinical Pharmacology Group, Pharmacy and Medicines Directorate St George’s University Hospitals NHS Foundation Trust London United Kingdom – name: 4 Department of Neurology and Neurosurgery University Medical Center Utrecht Brain Center Utrecht University Utrecht the Netherlands |
| Author_xml | – sequence: 1 givenname: Ville orcidid: 0000-0001-6064-1588 surname: Karhunen fullname: Karhunen, Ville organization: Department of Epidemiology and Biostatistics School of Public Health Imperial College London London United Kingdom, Research Unit of Mathematical Sciences University of Oulu Finland, Center for Life Course Health Research University of Oulu Finland – sequence: 2 givenname: Mark K. orcidid: 0000-0002-7887-9014 surname: Bakker fullname: Bakker, Mark K. organization: Department of Neurology and Neurosurgery University Medical Center Utrecht Brain CenterUtrecht University Utrecht the Netherlands – sequence: 3 givenname: Ynte M. orcidid: 0000-0002-5396-2989 surname: Ruigrok fullname: Ruigrok, Ynte M. organization: Department of Neurology and Neurosurgery University Medical Center Utrecht Brain CenterUtrecht University Utrecht the Netherlands – sequence: 4 givenname: Dipender orcidid: 0000-0001-7312-7078 surname: Gill fullname: Gill, Dipender organization: Department of Epidemiology and Biostatistics School of Public Health Imperial College London London United Kingdom, Clinical Pharmacology and Therapeutics Section Institute of Medical and Biomedical Education and Institute for Infection and Immunity St George’s, University of London London United Kingdom, Clinical Pharmacology Group, Pharmacy and Medicines Directorate St George’s University Hospitals NHS Foundation Trust London United Kingdom, Novo Nordisk Research Centre Oxford Oxford United Kingdom – sequence: 5 givenname: Susanna C. orcidid: 0000-0003-0118-0341 surname: Larsson fullname: Larsson, Susanna C. organization: Unit of Medical Epidemiology Department of Surgical Sciences Uppsala University Uppsala Sweden, Unit of Cardiovascular and Nutritional Epidemiology Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden |
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| SubjectTerms | Diabetes Mellitus, Type 2 Genome-Wide Association Study Humans Hypertension intracranial aneurysm Intracranial Aneurysm - epidemiology Intracranial Aneurysm - genetics lifestyle Mendelian randomization Mendelian Randomization Analysis Original Research Risk Factors single‐nucleotide polymorphisms Sleep Initiation and Maintenance Disorders subarachnoid hemorrhage Subarachnoid Hemorrhage - epidemiology Subarachnoid Hemorrhage - genetics |
| Title | Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study |
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