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Stroke genetics

Final Activity Report Summary - STROKENETICS (Stroke genetics)

Stroke, a 'brain attack' cutting off vital blood to the brain cells, is the second cause of death worldwide but the leading cause of death in Portugal. Stroke is even more disabling than lethal and requires more effective prevention and treatment strategies. It is a complex disease resulting from the interplay of environmental and genetic factors, but very few genetic factors for the common form of stroke have been identified. To identify additional susceptibility genes we are conducting the novel 'genomic convergence' approach combining data from whole-genome linkage screens with data from gene profiling analyses to determine which genes will be tested in association studies.

Our biobank with clinical information and biological samples has grown actively and we conducted gene expression analyses in peripheral blood mononuclear cells of carefully matched cases and controls. Preliminary data from 5 cases and 6 controls identified 82 genes differentially expressed among both 'young' cases vs. 'young' controls (45-54y) and 'old' cases vs. 'old' controls (65-74y) with a 1.5 fold-change cut-off. Phosphodiesterase 4D (PDE4D), currently the strongest genetic risk factor known for stroke, emerged as the only gene differentially expressed mapping to the 5q12 linkage peak identified in the Icelandic population, validating this approach. We also identified a set of genes orthologous to rat genes mapping to linkage peaks in animal studies which will be prioritised for testing in association studies.