Marios K. Georgakis, MD, PhD, Mass General Hospital, Harvard Medical School, Boston, MA & LMU Munich University Hospital, Munich, Germany, discusses his work looking at the genetic architecture of stroke of undetermined source. Cryptogenic stroke represents 30% of ischemic stroke cases and the lack of etiological diagnosis makes it difficult to know how to treat for prevention of further strokes. Genome wide data from over 16,000 ischemic stroke cases, including 4500 cases with undetermined etiology, and more than 32,000 controls were assessed to investigate the genetic overlap of stroke of undetermined source with large-artery atherosclerotic (LAAS), cardioembolic (CES), and small-vessel stroke (SVS). There was a strong genetic overlap between stroke of undetermined source and LAAS, CES, and CVS, suggesting many cases of cryptogenic stroke are underdiagnosed cases of these known subtypes. Additionally, genetic determinants of classical vascular risk factors, such as blood pressure, diabetes, inflammatory pathways, and obesity, were associated with stroke of undetermined source. The overlap in genetic and vascular risk factors between stroke of undermined source and known stroke etiologies highlights the limitations of current subtyping approaches. This interview took place at European Stroke Organisation Conference 2022 in Lyon, France.