| Autor: |
Ikram MA; 1 Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.; 2 Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands.; 3 Department of Neurology, Erasmus MC, Rotterdam, the Netherlands., Zonneveld HI; 1 Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.; 2 Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands., Roshchupkin G; 2 Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands.; 4 Department of Medical Informatics, Erasmus MC, Rotterdam, the Netherlands., Smith AV; 5 Icelandic Heart Association, Kopavogur, Iceland.; 6 Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Franco OH; 1 Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands., Sigurdsson S; 5 Icelandic Heart Association, Kopavogur, Iceland., van Duijn C; 1 Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands., Uitterlinden AG; 7 Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands., Launer LJ; 8 Intramural Research Program, NIA, NIH, Bethesda, MD, USA., Vernooij MW; 1 Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.; 2 Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands., Gudnason V; 5 Icelandic Heart Association, Kopavogur, Iceland.; 6 Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Adams HH; 1 Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.; 2 Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands. |
| Abstrakt: |
Cerebral blood flow is an important process for brain functioning and its dysregulation is implicated in multiple neurological disorders. While environmental risk factors have been identified, it remains unclear to what extent the flow is regulated by genetics. Here we performed heritability and genome-wide association analyses of cerebral blood flow in a population-based cohort study. We included 4472 persons free of cortical infarcts who underwent genotyping and phase-contrast magnetic resonance flow imaging (mean age 64.8 ± 10.8 years). The flow rate, cross-sectional area of the vessel, and flow velocity through the vessel were measured in the basilar artery and bilateral carotids. We found that the flow rate of the basilar artery is most heritable (h2 (SE) = 24.1 (9.8), p-value = 0.0056), and this increased over age. The association studies revealed two significant loci for the right carotid artery area (rs12546630, p-value = 2.0 × 10 -8 ) and velocity (rs2971609, p-value = 1.4 × 10 -8 ), with the latter showing a concordant effect in an independent sample (N = 1350, p-value = 0.057, meta-analyzed p-value = 2.5 × 10 -9 ). These loci were also associated with other cerebral blood flow parameters below genome-wide significance, and rs2971609 lies in a known migraine locus. These findings establish that cerebral blood flow is under genetic control with potential relevance for neurological diseases. |
