IntroductionMoyamoya disease (MMD) is a chronic cerebrovascular steno-occlusive disease of largely unknown etiology. Variants in theRNF213gene are strongly associated with MMD in East-Asia. In MMD patients of Northern-European origin, no predominant susceptibility variants have been identified so far.Research questionAre there specific candidate genes associated with MMD of Northern-European origin, including the knownRNF213gene? Can we establish a hypothesis for MMD phenotype and associated genetic variants identified for further research?Material and methodsAdult patients of Northern-European origin, treated surgically for MMD at Oslo University Hospital between October 2018 to January 2019 were asked to participate. WES was performed, with subsequent bioinformatic analysis and variant filtering. The selected candidate genes were either previously reported in MMD or known to be involved in angiogenesis. The variant filtering was based on variant type, location, population frequency, and predicted impact on protein function.ResultsAnalysis of WES data revealed nine variants of interest in eight genes. Five of those encode proteins involved in nitric oxide (NO) metabolism:NOS3,NR4A3, ITGAV, GRB7andAGXT2. In theAGXT2gene, ade novovariant was detected, not previously described in MMD. None harboured the p.R4810K missense variant in theRNF213gene known to be associated with MMD in East-Asian patients.Discussion and conclusionOur findings suggest a role for NO regulation pathways in Northern-European MMD and introduceAGXT2as a new susceptibility gene. This pilot study warrants replication in larger patient cohorts and further functional investigations.