The Familial Intracranial Aneurysm (FIA) study protocol

Broderick, Joseph P.; Sauerbeck, Laura; Foroud, Tatiana; Huston, John; Pankratz, Nathan; Meissner, Irene; Brown, Robert D.

doi:10.1186/1471-2350-6-17

Cited by 64 publications

(48 citation statements)

References 54 publications

(30 reference statements)

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“…Most of the aneurysms were small: 2 IAs were ≥7 mm in maximal diameter; 19 were 4-6 mm; and 50 were 2-3 mm. Aneurysms arose most commonly on the ICA, with 31 such lesions (8 OphA, and 23 other ICA), followed in frequency by the MCA (20), PCoA (8), anterior cerebral artery (7), ACoA (3), and other locations (2).…”

Section: Resultsmentioning

confidence: 99%

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Screening for brain aneurysm in the Familial Intracranial Aneurysm study: frequency and predictors of lesion detection

Brown

Huston

Hornung

et al. 2008

JNS

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102

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Object-Approximately 20% of patients with an intracranial saccular aneurysm report a family history of intracranial aneurysm (IA) or subarachnoid hemorrhage. A better understanding of predictors of aneurysm detection in familial IA may allow more targeted aneurysm screening strategies. Methods-TheFamilial Intracranial Aneurysm (FIA) study is a multicenter study, in which the primary objective is to define the susceptibility genes related to the formation of IA. First-degree relatives (FDRs) of those affected with IA are offered screening with magnetic resonance (MR) angiography if they were previously unaffected, are ≥ 30 years of age, and have a history of smoking and/or hypertension. Independent predictors of aneurysm detection on MR angiography were determined using the generalized estimating equation version of logistic regression.Results-Among the first 303 patients screened with MR angiography, 58 (19.1%) had at least 1 IA, including 24% of women and 11.7% of men. Ten (17.2%) of 58 affected patients had multiple aneurysms. Independent predictors of aneurysm detection included female sex (odds ratio [OR] 2.46, p = 0.001), pack-years of cigarette smoking (OR 3.24 for 20 pack-years of cigarette smoking compared with never having smoked, p < 0.001), and duration of hypertension (OR 1.26 comparing those with 10 years of hypertension to those with no hypertension, p = 0.006).Conclusions-In the FIA study, among the affected patients' FDRs who are > 30 years of age, those who are women or who have a history of smoking or hypertension are at increased risk of suffering an IA and should be strongly considered for screening. To clarify further the occurrence of IA detection on brain MR angiography studies in families with several members affected, we report the initial results of MR angiography screening of FDRs-siblings, parents, and children-of those affected with an IA in a multicenter study of familial IA. We also report the predictors of IA detection on brain MR angiography among these FDRs. Clinical Materials and MethodsThe FIA study is an international, multicenter study including 26 clinical centers, which represents 41 recruitment sites in North America, New Zealand, and Australia. 2 The study was approved by the institutional review board/ethics committee at each of the study centers and recruitment sites.Families with multiple members in whom IAs were diagnosed were enrolled to identify the chromosomal regions associated with an increased risk of IA and to determine the effects of environmental factors on the expression of genes within these regions. Individuals with either ruptured or unruptured IAs were considered to have the phenotype. Patients were excluded if they had a fusiform IA; an intranidal aneurysm with an arteriovenous malformation; a family history of polycystic kidney disease, Ehlers-Danlos syndrome, Marfan syndrome, fibromuscular dysplasia, or moyamoya syndrome; or if informed consent could not be obtained from the patient or family members.Detailed medical records and the informa...

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Section: Resultsmentioning

confidence: 99%

“…2 The study was approved by the institutional review board/ethics committee at each of the study centers and recruitment sites.…”

Section: Clinical Materials and Methodsmentioning

confidence: 99%

Screening for brain aneurysm in the Familial Intracranial Aneurysm study: frequency and predictors of lesion detection

Brown

Huston

Hornung

et al. 2008

JNS

Self Cite

102

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“…[3][4][5] Furthermore, several studies suggested an increased occurrence of IA and SAH in first-and second-degree relatives of SAH, with the incidence rate of 6-10%. [6][7][8][9] Several Mendelian disorders, such as autosomal-dominant polycystic kidney disease and Ehlers-Danlos syndrome type IV are associated with an increased risk of IA formation. 10,11 All these evidence fortified the roles of genetic factors in the pathogenesis of IA.…”

Section: Introductionmentioning

confidence: 99%

Impact of LIMK1, MMP2 and TNF-α variations for intracranial aneurysm in Japanese population

et al. 2011

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Genetic factors are known to have an important role in intracranial aneurysm (IA) pathogenesis. The purpose of this study is to identify single-nucleotide polymorphisms (SNPs) that are associated with IA in Japanese population. A total of 2050 IA patients and 1835 controls recruited in Biobank Japan, The University of Tokyo were used in this study. In all, 45 SNPs in 24 genes encoding proteins, which have been considered to be possible risk factors to IA pathogenesis, were genotyped using multiplex PCR-invader assay. Association analysis was evaluated by logistic regression analysis before and after adjustment of age, smoking and hypertension status. This case-control association study revealed a SNP, rs6460071 located on LIMK1 gene (P¼0.00069) to be significantly associated with increased risk of IA. In addition, two SNPs, rs243847 (P¼0.00086) and rs243865 (P¼0.00090), on matrix metallopeptidase 2 (MMP2) gene and one SNP rs1799724 (P¼0.0026) on tumor necrosis factor-a (TNF-a) gene, are marginally associated with IA in male-and female-specific manner, respectively. In conclusion, a large-scale case-control association study was conducted to verify genetic variations associated with IA in Japanese population. This study gave insights on the importance of stratified analysis between genders, and suggested that the underlying mechanism of IA pathogenesis might differ between females and males.

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“…The investigators' first goal will be to carry out a 10-cM genome screen to identify familial IA susceptibility loci (Broderick et al 2005). With a sample size of this magnitude, many further studies could lead to meaningful results.…”

Section: Chromosomal Loci Mapped By Linkage Studiesmentioning

confidence: 99%

The genetics of intracranial aneurysms

Krischek

Inoue

2006

J Hum Genet

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The rupture of an intracranial aneurysm (IA) leads to a subarachnoid hemorrhage, a sudden onset disease that can lead to severe disability and death. Several risk factors such as smoking, hypertension and excessive alcohol intake are associated with subarachnoid hemorrhage. IAs, ruptured or unruptured, can be treated either surgically via a craniotomy (through an opening in the skull) or endovascularly by placing coils through a catheter in the femoral artery. Even though the etiology of IA formation is mostly unknown, several studies support a certain role of genetic factors. In reports so far, genome-wide linkage studies suggest several susceptibility loci that may contain one or more predisposing genes. Studies of several candidate genes report association with IAs. To date, no single gene has been identified as responsible for IA formation or rupture. The identification of susceptible genes may lead to the understanding of the mechanism of formation and rupture and possibly lead to the development of a pharmacological therapy.

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The Familial Intracranial Aneurysm (FIA) study protocol

Cited by 64 publications

References 54 publications

Screening for brain aneurysm in the Familial Intracranial Aneurysm study: frequency and predictors of lesion detection

Screening for brain aneurysm in the Familial Intracranial Aneurysm study: frequency and predictors of lesion detection

Impact of LIMK1, MMP2 and TNF-α variations for intracranial aneurysm in Japanese population

The genetics of intracranial aneurysms

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