Modifiable risk factors for intracranial aneurysm and aneurysmal subarachnoid hemorrhage: A mendelian randomization study
Karhunen, Ville; Bakker, Mark K.; Ruigrok, Ynte M.; Gill, Dipender; Larsson, Susanna C.
(2021) Journal of the American Heart Association, volume 10, issue 22, pp. 1 - 8
(Article)
Abstract
BACKGROUND: The aim of this study was to assess the associations of modifiable lifestyle factors (smoking, coffee consump-tion, 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
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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 hori-zontal 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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Keywords: Intracranial aneurysme, Lifestyle, Mendelian randomization, Risk factors, Single-nucleotide polymorphisms, Subarachnoid hemorrhag, Cardiology and Cardiovascular Medicine, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 2047-9980
Publisher: Wiley-Blackwell
Note: Funding Information: Gill and Karhunen are supported by the British Heart Foundation Centre of Research Excellence (RE/18/4/34215) at Imperial College London. Karhunen is supported by the Academy of Finland Project 312123, and European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 848158. Gill is supported by a National Institute for Health Research Clinical Lectureship at St. George’s, University of London (CL-2020-16-001). Larsson acknowledges research support from the Swedish Research Council for Health, Working Life and Welfare (Forte, 2018-00123), the Swedish Heart-Lung Foundation (Hjärt-Lungfonden, 20190247), and the Swedish Research Council (Vetenskapsrådet, 2019-00977). Bakker was supported by the Netherlands Cardiovascular Research Initiative: An initiative with support of the Dutch Heart Foundation, CVON2015-08 ERASE. Ruigrok received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (PRYSM, grant agreement No. 852173). Funding Information: The authors would like to thank the International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm working group. Data on glycemic traits have been contributed by the Meta-Analyses of Glucose and Insulin-related traits Consortium investigators and have been downloaded from www.magic? inves?tigat?ors.org. We acknowledge the Chronic Kidney Disease Genetics (CKDGen) Consortium for releasing GWAS summary data. Gill and Karhunen are supported by the British Heart Foundation Centre of Research Excellence (RE/18/4/34215) at Imperial College London. Karhunen is supported by the Academy of Finland Project 312123, and European Union?s Horizon 2020 research and innovation programme under Grant Agreement No 848158. Gill is supported by a National Institute for Health Research Clinical Lectureship at St. George?s, University of London (CL-2020-16-001). Larsson acknowledges research support from the Swedish Research Council for Health, Working Life and Welfare (Forte, 2018-00123), the Swedish Heart-Lung Foundation (Hj?rt-Lungfonden, 20190247), and the Swedish Research Council (Vetenskapsr?det, 2019-00977). Bakker was supported by the Netherlands Cardiovascular Research Initiative: An initiative with support of the Dutch Heart Foundation, CVON2015-08 ERASE. Ruigrok received funding from the European Research Council (ERC) under the European Union?s Horizon 2020 research and innovation programme (PRYSM, grant agreement No. 852173). Publisher Copyright: © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
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