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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Autores principales:	Ville Karhunen, Mark K. Bakker, Ynte M. Ruigrok, Dipender Gill, Susanna C. Larsson
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	intracranial aneurysm lifestyle Mendelian randomization risk factors single‐nucleotide polymorphisms subarachnoid hemorrhage Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/67d4130268b94c69bf2c9bb3c053bd41
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spelling	oai:doaj.org-article:67d4130268b94c69bf2c9bb3c053bd412021-11-16T10:22:43ZModifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study10.1161/JAHA.121.0222772047-9980https://doaj.org/article/67d4130268b94c69bf2c9bb3c053bd412021-11-01T00:00:00Zhttps://www.ahajournals.org/doi/10.1161/JAHA.121.022277https://doaj.org/toc/2047-9980Background 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.Ville KarhunenMark K. BakkerYnte M. RuigrokDipender GillSusanna C. LarssonWileyarticleintracranial aneurysmlifestyleMendelian randomizationrisk factorssingle‐nucleotide polymorphismssubarachnoid hemorrhageDiseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 10, Iss 22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	intracranial aneurysm lifestyle Mendelian randomization risk factors single‐nucleotide polymorphisms subarachnoid hemorrhage Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	intracranial aneurysm lifestyle Mendelian randomization risk factors single‐nucleotide polymorphisms subarachnoid hemorrhage Diseases of the circulatory (Cardiovascular) system RC666-701 Ville Karhunen Mark K. Bakker Ynte M. Ruigrok Dipender Gill Susanna C. Larsson Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study
description	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.
format	article
author	Ville Karhunen Mark K. Bakker Ynte M. Ruigrok Dipender Gill Susanna C. Larsson
author_facet	Ville Karhunen Mark K. Bakker Ynte M. Ruigrok Dipender Gill Susanna C. Larsson
author_sort	Ville Karhunen
title	Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study
title_short	Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study
title_full	Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study
title_fullStr	Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study
title_full_unstemmed	Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study
title_sort	modifiable risk factors for intracranial aneurysm and aneurysmal subarachnoid hemorrhage: a mendelian randomization study
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/67d4130268b94c69bf2c9bb3c053bd41
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Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study

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