Both PITX2 and ZFHX3 were originally identified as risk factors for atrial fibrillation.8, 9 Atrial fibrillation is a major risk factor for stroke, particularly in the elderly, and therefore their association with ischaemic stroke is not unexpected. Our results confirm this association and clearly show that it is limited to the cardioembolic stroke subtype. Furthermore, we were able to show an association between PITX2 and ischaemic stroke in prospective cohorts. A potential bias is that a variant that is in fact associated with mortality rate after acute stroke and not with stroke risk might seem to be related to risk; for cross-sectional studies in a disease such as stroke, which has substantial early mortality, death might occur before or soon after hospital admission before samples are taken. In a prospective study, such cases are included as the sample was taken at recruitment to the study and therefore before the onset of stroke.
