| 1. |
- Bakker, M. K., et al.
(författare)
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Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:12, s. 1303-1313
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Tidskriftsartikel (refereegranskat)abstract
- Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits. Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.
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| 2. |
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| 3. |
- Helgadottir, Anna, et al.
(författare)
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The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
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| 4. |
- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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| 5. |
- Rannikmäe, K., et al.
(författare)
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Reliability of intracerebral hemorrhage classification systems: A systematic review
- 2016
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 11:6, s. 626-636
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accurately distinguishing non-traumatic intracerebral hemorrhage (ICH) subtypes is important since they may have different risk factors, causal pathways, management, and prognosis. We systematically assessed the inter- and intra-rater reliability of ICH classification systems. Methods: We sought all available reliability assessments of anatomical and mechanistic ICH classification systems from electronic databases and personal contacts until October 2014. We assessed included studies’ characteristics, reporting quality and potential for bias; summarized reliability with kappa value forest plots; and performed meta-analyses of the proportion of cases classified into each subtype. Summary of review: We included 8 of 2152 studies identified. Inter- and intra-rater reliabilities were substantial to perfect for anatomical and mechanistic systems (inter-rater kappa values: anatomical 0.78–0.97 [six studies, 518 cases], mechanistic 0.89–0.93 [three studies, 510 cases]; intra-rater kappas: anatomical 0.80–1 [three studies, 137 cases], mechanistic 0.92–0.93 [two studies, 368 cases]). Reporting quality varied but no study fulfilled all criteria and none was free from potential bias. All reliability studies were performed with experienced raters in specialist centers. Proportions of ICH subtypes were largely consistent with previous reports suggesting that included studies are appropriately representative. Conclusions: Reliability of existing classification systems appears excellent but is unknown outside specialist centers with experienced raters. Future reliability comparisons should be facilitated by studies following recently published reporting guidelines. © 2016, © 2016 World Stroke Organization.
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| 6. |
- van Dijk, B. J., et al.
(författare)
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Complement C5 Contributes to Brain Injury After Subarachnoid Hemorrhage
- 2020
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Ingår i: Translational Stroke Research. - : Springer Science and Business Media LLC. - 1868-4483 .- 1868-601X. ; 11, s. 678-688
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies showed that complement activation is associated with poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH). We investigated whether complement activation is underlying brain injury after aneurysmal SAH (n=7) and if it is an appropriate treatment target. We investigated complement expression in brain tissue of aneurysmal SAH patients (n =930) and studied the role of common genetic variants in C3 and C5 genes in outcome. We analyzed plasma levels (n =229) to identify the functionality of a single nucleotide polymorphism (SNP) associated with outcome. The time course of C5a levels was measured in plasma (n =31) and CSF (n =10). In an SAH mouse model, we studied the extent of microglia activation and cell death in wild-type mice, mice lacking the C5a receptor, and in mice treated with C5-specific antibodies (n=15 per group). Brain sections from aneurysmal SAH patients showed increased presence of complement components C1q and C3/C3b/iC3B compared to controls. The complement component 5 (C5) SNP correlated with C5a plasma levels and poor disease outcome. Serial measurements in CSF revealed that C5a was >1400-fold increased 1 day after aneurysmal SAH and then gradually decreased. C5a in plasma was 2-fold increased at days 3–10 after aneurysmal SAH. In the SAH mouse model, we observed a ≈40% reduction in both microglia activation and cell death in mice lacking the C5a receptor, and in mice treated with C5-specific antibodies. These data show that C5 contributes to brain injury after experimental SAH, and support further study of C5-specific antibodies as novel treatment option to reduce brain injury and improve prognosis after aneurysmal SAH.
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