AUTHOR=Huang Lihong , Tang Jiaqi , Lin Lijuan , Wang Ruihan , Chen Feng , Wei Yongyue , Si Yi , Fu Weiguo 

TITLE=Association of genetic variants in ULK4 with the age of first onset of type B aortic dissection

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.956866

DOI=10.3389/fgene.2022.956866

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> The association between autophagy, structural alterations of the aortic wall, and endothelial dysfunction in humans has yet to be fully elucidated. The family of <italic>ULK</italic> (UNC51-like) enzymes plays critical roles in autophagy and development. This study aimed to evaluate the association between <italic>ULK</italic> gene family members and patient age of first type B aortic dissection (TBAD) onset.</p><p><bold>Methods:</bold> The genotype data in a TBAD cohort from China and the related summary-level datasets were analyzed. We applied the sequence kernel association test (SKAT) to test the association between single-nucleotide polymorphisms (SNPs) and age of first onset of TBAD controlling for gender, hypertension, and renal function. Next, we performed a 2-sample Mendelian randomization (MR) to explore the potential causal relationship between <italic>ULK4</italic> and early onset of TBAD at the level of gene expression coupled with DNA methylation with genetic variants as instrumental variables.</p><p><bold>Results:</bold> A total of 159 TBAD patients with 1,180,097 SNPs were included. Concerning the association between the <italic>ULK</italic> gene family and the age of first onset of the TBAD, only <italic>ULK4</italic> was found to be significant according to SKAT analysis (q-<italic>FDR</italic> = 0.0088). From 2-sample MR, the high level of <italic>ULK4</italic> gene expression was related to a later age of first onset of TBAD (<italic>β</italic> = 4.58, <italic>p</italic> = 0.0214).</p><p><bold>Conclusion:</bold> This is the first study of the <italic>ULK</italic> gene family in TBAD, regarding the association with the first onset age. We demonstrated that the <italic>ULK4</italic> gene is associated with the time of onset of TBAD based on both the SKAT and 2-sample MR analyses.</p>