Increased Prevalence of Microangiopathic Brain Lesions among Siblings of Patients with Lacunar Stroke

Leistner, Stefanie; Huebner, Norbert; Faulstich, Andreas; Ludwig, Daniela; Rees, Maren; Marx, Peter; Langer, B.; Nikolova, Alexandrina; Hartmann, Andreas; Koennecke, Hans–Christian

doi:10.1159/000111877

Cited by 4 publications

(3 citation statements)

References 52 publications

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“…The authors speculate that impaired endothelial function in blacks can be one of the possible genetic mechanisms responsible for the predominance of SVD-related strokes in the black population. Other studies can be found in the literature showing that genetic mechanisms play a role in the susceptibility to develop lacunar strokes and syndromes, 20 with different genes being involved. [21][22][23] Some interesting observations can be derived from our study regarding the correlation between ethnicity and TEE findings.…”

Section: Discussionmentioning

confidence: 99%

Ethnic Differences in Ischemic Stroke of Working Age in Northern Israel

Telman

Kouperberg

Sprecher

et al. 2010

Journal of Stroke and Cerebrovascular Diseases

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Section: Discussionmentioning

confidence: 99%

Ethnic Differences in Ischemic Stroke of Working Age in Northern Israel

Telman

Kouperberg

Sprecher

et al. 2010

Journal of Stroke and Cerebrovascular Diseases

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“…Arguments for similar subtypes of stroke in family-members can be found in the literature, for example high heritability of white matter lesions – one of the features of lacunar stroke - in the Framingham Heart Study,[14] more concordant monozygotic than dizygotic twins for white matter lesions,[15] and high prevalence of micro-angiopathic lesions in siblings of lacunar stroke patients [16]. However, we acknowledge that at least some surplus of the stroke in FDR will have different etiology, e.g.…”

Section: Discussionmentioning

confidence: 95%

Estimating the Magnitude of Genetic Factors by Calculating the Genetic Relative Risk of Stroke in First-Ever Lacunar Stroke Patients

et al. 2011

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BackgroundPositive family history of stroke is an independent risk factor for lacunar stroke. However, the magnitude of familial aggregation of a certain disease is better evaluated by the genetic relative risk. This is calculated by dividing the prevalence of specific disease in family members of patients by the prevalence of this disease in the general population. In a cohort of lacunar stroke patients, who were subtyped clinically and radiologically, we determined the genetic relative risk of stroke.MethodsBy questionnaire and additional interview, we obtained a complete first-degree family history of stroke. The prevalence of stroke in first-degree relatives of these lacunar stroke patients was compared to the self-reported prevalence of stroke in a Dutch community based cohort of elderly volunteers. Secondly, the influence of proband characteristics and family composition on parental and sibling history of stroke were evaluated.Principal FindingsWe collected data of 1066 first-degree relatives of 195 lacunar stroke patients. Strokes occurred in 13.5% of first-degree relatives. The genetic relative risk was 2.94 (95%CI 2.45–3.53) for overall first-degree relatives, 4.52 (95%CI 3.61–5.65) for patients' parents and 2.10 (95%CI 1.63–2.69) for patients' siblings. Age of proband and proband status for hypertension influenced the chance of having a parent with a history of stroke whereas the likelihood of having a concordant sibling increased with sibship size.ConclusionsWe found an increased genetic relative risk of stroke in first-degree relatives of patients with lacunar stroke. Our data warrant further genomic research in this well-defined high risk population for stroke.

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“…A genetic component is suggested by increased risk of covert MRI-infarcts among individuals whose parents or siblings have experienced clinically overt infarcts 4,5. As we will detail, previous candidate gene studies of covert MRI-infarcts have yielded inconsistent findings.…”

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confidence: 91%

Genome-Wide Association Studies of MRI-Defined Brain Infarcts

Debette

Bis

Fornage

et al. 2010

Stroke

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Background and Purpose-Previous studies examining genetic associations with MRI-defined brain infarct have yielded inconsistent findings. We investigated genetic variation underlying covert MRI infarct in persons without histories of transient ischemic attack or stroke. We performed meta-analysis of genome-wide association studies of white participants in 6 studies comprising the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Methods-Using 2.2 million genotyped and imputed single nucleotide polymorphisms, each study performed crosssectional genome-wide association analysis of MRI infarct using age-and sex-adjusted logistic regression models. 2 Although the majority of these MRI infarcts do not produce acute clinical symptoms leading to a diagnosis of stroke, they cannot be considered benign, silent, or asymptomatic, because they are associated with an increased risk for cognitive deficits, motor impairments, and future stroke. 2 The pathogenesis of these covert brain infarcts remains poorly understood.Whereas several monogenic disorders are known to cause brain infarcts, the genes underlying brain infarcts in the general population remain undetermined. 3 A genetic component is suggested by increased risk of covert MRI infarcts among individuals whose parents or siblings have experienced clinically overt infarcts. 4,5 Previous candidate gene studies of covert MRI infarcts have yielded inconsistent findings. Genome-wide association studies (GWAS) of MRI infarcts are lacking and would permit an unbiased search for genetic variants associated with this phenotype, without relying on a priori hypotheses about underlying pathophysiology. 6 To study genetics of these infarcts, we adapted an analytic approach used in a previous study 7 of stroke from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and combined GWAS from 6 prospective population-based cohort studies: the Aging GeneEnvironment Susceptibility-Reykjavik Study (AGESReykjavik); the Atherosclerosis Risk in Communities (ARIC) Study; the Austrian Stroke Prevention Study (ASPS); the Cardiovascular Health Study (CHS); the Framingham Heart Study (FHS); and the Rotterdam Study. We present results from this meta-analysis that included 9401 stroke-free white participants. Materials and Methods ConsortiumThe CHARGE consortium includes large prospective communitybased cohort studies having genome-wide variation data coupled with extensive data on multiple phenotypes. 8 All participating studies agreed on phenotype harmonization, covariate selection, prespecified analytic plans for within-study analyses, and meta-analysis of results. Each study secured approval from Institutional Review Boards, and all participants provided written informed consent for study participation, MRI scanning, and use of DNA for genetic research. SettingDetails of cohort selection, risk factor assessment, and outcome determination in the 6 studies have been reported previously (supplemental Appendix, section 1, available o...

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Increased Prevalence of Microangiopathic Brain Lesions among Siblings of Patients with Lacunar Stroke

Cited by 4 publications

References 52 publications

Ethnic Differences in Ischemic Stroke of Working Age in Northern Israel

Ethnic Differences in Ischemic Stroke of Working Age in Northern Israel

Estimating the Magnitude of Genetic Factors by Calculating the Genetic Relative Risk of Stroke in First-Ever Lacunar Stroke Patients

Genome-Wide Association Studies of MRI-Defined Brain Infarcts

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