Abstract
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.
Highlights
Up till studies on genetic epidemiology of stroke consisted mostly of family history (FH) studies, which defined positive FH of stroke as the presence of at least one affected first-degree relative (FDR)
Studies on genetic epidemiology of stroke consisted mostly of family history (FH) studies, which defined positive FH of stroke as the presence of at least one affected first-degree relative (FDR). These studies found an association between FH of stroke and lacunar stroke, with odds ratios varying from 1.79 to 2.76.[1,2,3] As the chance of the presence of a common disease in a family increases with family size, a better approach to evaluate the magnitude of the contribution of genetic factors in a certain disease is to estimate the genetic relative risk (GRR), called recurrence risk ratio
Participants The consecutive registration of residential stroke patients from May 2003 until December 2007 at the Maastricht University Medical Centre (MUMC) was described earlier.[6]. From this registry lacunar stroke patients were included if they had a firstever lacunar stroke, which was defined as (1) one of the recognized lacunar syndromes with a lesion on imaging compatible with the occlusion of a single perforating artery or if no such lesion was visible on imaging, (2) established criteria of unilateral motor and/ or sensory signs that involved the whole of at least 2 of the 3 body parts without disturbance of consciousness or cortical functions were used.[7]
Summary
Studies on genetic epidemiology of stroke consisted mostly of family history (FH) studies, which defined positive FH of stroke as the presence of at least one affected first-degree relative (FDR) These studies found an association between FH of stroke and lacunar stroke, with odds ratios varying from 1.79 to 2.76.[1,2,3] As the chance of the presence of a common disease in a family increases with family size, a better approach to evaluate the magnitude of the contribution of genetic factors in a certain disease is to estimate the genetic relative risk (GRR), called recurrence risk ratio (lR). 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
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