Altered methylation pattern in EXOC4 is associated with stroke outcome: an epigenome-wide association study

Cullell N, Soriano-Tárraga C, Gallego-Fábrega C, Cárcel-Márquez J, Muiño E, Llucià-Carol L, Lledós M, Esteller M, de Moura MC, Montaner J et al. Clin Epigenetics. 2022 Sep 30;14(1):124. doi: 10.1186/s13148-022-01340-5.PMID: 36180927
Results: The meta-analysis revealed an epigenome-wide signifcant association in EXOC4 (p value=8.4× 10–08) and in MERTK (p value=1.56× 10–07). Only the methylation in EXOC4 was also associated in the Discovery and in the Replication Cohorts (p value=1.14× 10–06 and p value=1.3× 10–02, respectively). EXOC4 methylation negatively correlated with the long-term outcome (coefcient=−4.91) and showed a tendency towards a decrease in EXOC4 expression (rho=−0.469, p value=0.091). Pathway enrichment from the meta-analysis revealed signifcant associa‑tions related to the endocytosis and deubiquitination processes. Seventy-nine plasma proteins were diferentially expressed in association with EXOC4 methylation. Pathway analysis of these proteins showed an enrichment in natural killer (NK) cell activation. The cell-type methylation analysis in blood also revealed a diferential methylation in NK cells.
Acknowledgements: We thank the International Stroke Genetics Consortium, the Spanish Stroke Genetics Consortium, the International Stroke Genetics Consor‑tium, the Global Alliance for Stroke acute and long-term outcome, RETICS Network INVICTUS (RD16/0019/0002, RD16/0019/0010, RD16/0019/0011, RD16/0019/0021) and the RICORS Stroke network.