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Identification of 20 novel loci associated with ischaemic stroke. Epigenome-wide association study

2020; Landes Bioscience; Volume: 15; Issue: 9 Linguagem: Inglês

10.1080/15592294.2020.1746507

1559-2308

Carolina Soriano‐Tárraga, Uxue Lazcano, Eva Giralt‐Steinhauer, Carla Avellaneda-Gómez, Ángel Ois, Ana Rodríguez-Campello, Elisa Cuadrado‐Godia, Alejandra Gómez-González, Alba Fernández‐Sanlés, Roberto Elosúa, Israel Fernández‐Cadenas, Natàlia Cullell, Joan Montaner, Sebastián Morán, Manel Esteller, Jordi Jiménez-Conde, Jaume Roquer,

Genetic Associations and Epidemiology

DNA methylation is dynamic, varies throughout the life course, and its levels are influenced by lifestyle and environmental factors, as well as by genetic variation. The leading genetic variants at stroke risk loci identified to date explain roughly 1–2% of stroke heritability. Most of these single nucleotide polymorphisms are situated within a regulatory sequence marked by DNase I hypersensitivity sites, which would indicate involvement of an epigenetic mechanism. To detect epigenetic variants associated with stroke occurrence and stroke subtypes.A two-stage case–control epigenome-wide association study was designed. The discovery sample with 401 samples included 218 ischaemic stroke (IS) patients, assessed at Hospital del Mar (Barcelona, Spain) and 183 controls from the REGICOR cohort. In two independent samples (N = 226 and N = 166), we replicated 22 CpG sites differentially methylated in IS in 21 loci, including 2 CpGs in locus ZFHX3, which includes known genetic variants associated with stroke. The pathways associated with these loci are inflammation and angiogenesis. The meta-analysis identified 384 differentially methylated CpGs, including loci of known stroke and vascular risk genetic variants, enriched by loci involved in lipid metabolism, adipogenesis, circadian clock, and glycolysis pathways.We identified a set of 22 CpGs in 21 loci associated with IS. Our analysis suggests that DNA methylation changes may contribute to orchestrating gene expression that contributes to IS.