Chromatin architecture around stroke haplotypes provides evidence that genetic risk is conferred through vascular cells

Plain language summary Previous studies have found several variations in the DNA sequence (known as single nucleotide polymorphisms) linked to higher stroke risk. But the mechanisms behind how they increase risk is unknown. One hypothesis is that they affect non-coding DNA elements (i.e., epigenetics), which in turn drive abnormal changes in gene expression leading to increased stroke risk. To investigate this potential mechanism, we mined publicly available, cell-type specific databases. We searched for overlap between the regions with polymorphisms and regions where DNA transcription machinery bind (i.e., enhancers, transcription factor binding sites). We found that fibroblasts and smooth muscle cells (cells in vessel walls) had more of these DNA elements in regions associated with stroke risk. Bioinformatics analyses of genes that could be affected by changes in these elements were linked to stroke-related mechanisms.