Integrated analysis identifies hypertension-GWAS-loci regulated, differentially expressed genes in aorta and blood of aortic dissection

Background: Aortic dissection is a life-threatening condition caused by a tear in the intimal layer of the aorta. Hypertension is the most common risk factor of aortic dissection. However, only a small proportion of subjects with hypertension will develop aortic dissection. Genetic basis and effect genes determining the development and progression of aortic dissection remained to be identified. In this study, we attempted to recognize the underlying effect genes from reliable large-scale genome-wide association studies (GWASs) of hypertension.Methods: As most GWAS locus functions through its biological role in gene expression regulation, we initially converted the GWAS signals to transcriptomic profiles in aorta using the Functional Summary-based Imputation (FUSION) algorithm. The FUSION derived genes were then checked whether they were differentially expressed in aorta of subjects with and without aortic dissection.Results: We found 23 genes that were regulated by hypertension GWAS loci and were altered in aorta of dissection patients. In particular, the DCAF16 gene could be detected in blood, providing a possibility of non-invasive early detection or prediction of hypertensive individuals at risk of aortic dissection.Conclusions: Our analyses identified effect genes in aorta and provided a possibility of non-invasive early detection of aortic dissection.Trial registration: Retrospectively registered.

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