Common Genetic Variation in Relation to Brachial Vascular Dimensions and Flow-Mediated Vasodilation

rachial artery dimensions and reactivity as assessed by flow-mediated dilation (FMD) using ultrasound have been associated with cardiovascular disease. 1 Systematic analysis of common genetic variation and brachial artery reactivity may help explain the hereditary component of vascular function.2 We performed an inverse variance weighting in a fixed effects meta-analysis of 6 genome-wide association studies on brachial artery diameter, maximum brachial artery diameter adjusted for baseline diameter, and FMD totaling 17 151 community-based individuals of European ancestry (Cardiovascular Health Study, Framingham Heart Study, GHS (Gutenberg Health Study), Prospective Investigation of the Vasculature in Uppsala Seniors, SHIP (Study of Health in Pomerania), and Young Finns Study).For replication, we genotyped up to 9555 independent individuals of the GHS using functionally tested standard 5´ nuclease assays on a 7900HT Fast Real-Time polymerase chain reaction system (Applied Biosystems).We selected 8 single nucleotide polymorphisms (SNPs; 6 for brachial artery diameter, 2 for maximum brachial artery diameter adjusted for baseline diameter, and 0 for FMD) with genome-wide significance or nominally significant regions with several supporting signals in the region and pathophysiological plausibility for replication by de novo genotyping in an independent GHS sample.Furthermore, we performed a stage 2 meta-analysis including all individuals.All studies were approved by the local ethics committees.Because of the sensitive nature of the data collected for this study, requests to access the dataset from qualified researchers trained in human subject confidentiality protocols may be sent to Dr med.Renate B.