Heritability and genome-wide associations studies of cerebral blood flow in the general population. Issue 9 (September 2018)

• Record Type: Journal Article
• Authors: Ikram, M Arfan; Zonneveld, Hazel I; Roshchupkin, Gennady; Smith, Albert V; Franco, Oscar H; Sigurdsson, Sigurdur; van Duijn, Cornelia; Uitterlinden, André G; Launer, Lenore J; Vernooij, Meike W; Gudnason, Vilmundur; Adams, Hieab HH
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 38:Issue 9(2018)
• Page Start: 1598
• Page End: 1608
• Publication Date: 2018-09
• Subjects: Aging -- cerebral blood flow -- genome-wide association study -- heritability -- population-based; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X17715861
• Languages: English
• ISSNs: 0271-678X

Abstract

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.