Identification of 20 novel loci associated with ischaemic stroke. Epigenome-wide association study
Por:
Soriano-Tarraga, C, Lazcano, U, Giralt-Steinhauer, E, Avellaneda-Gomez, C, Ois, A, Rodriguez-Campello, A, Cuadrado-Godia, E, Gomez-Gonzalez, A, Fernandez-Sanles, A, Elosua, R, Fernandez-Cadenas, I, Cullell, N, Montaner, J, Moran, S, Esteller, M, Jimenez-Conde, J
Publicada:
1 sep 2020
Ahead of Print:
1 abr 2020
Resumen:
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.
Filiaciones:
Soriano-Tarraga, C:
Univ Autonoma Barcelona, Univ Pompeu Fabra, IMIM Inst Hosp del Mar Invest Med, DCEXS,Hosp del Mar,Neurovasc Res Grp,Dept Neurol, Barcelona, Spain
Lazcano, U:
Univ Autonoma Barcelona, Univ Pompeu Fabra, IMIM Inst Hosp del Mar Invest Med, DCEXS,Hosp del Mar,Neurovasc Res Grp,Dept Neurol, Barcelona, Spain
Giralt-Steinhauer, E:
Univ Autonoma Barcelona, Univ Pompeu Fabra, IMIM Inst Hosp del Mar Invest Med, DCEXS,Hosp del Mar,Neurovasc Res Grp,Dept Neurol, Barcelona, Spain
Avellaneda-Gomez, C:
Univ Autonoma Barcelona, Univ Pompeu Fabra, IMIM Inst Hosp del Mar Invest Med, DCEXS,Hosp del Mar,Neurovasc Res Grp,Dept Neurol, Barcelona, Spain
Ois, A:
Univ Autonoma Barcelona, Univ Pompeu Fabra, IMIM Inst Hosp del Mar Invest Med, DCEXS,Hosp del Mar,Neurovasc Res Grp,Dept Neurol, Barcelona, Spain
Rodriguez-Campello, A:
Univ Autonoma Barcelona, Univ Pompeu Fabra, IMIM Inst Hosp del Mar Invest Med, DCEXS,Hosp del Mar,Neurovasc Res Grp,Dept Neurol, Barcelona, Spain
Cuadrado-Godia, E:
Univ Autonoma Barcelona, Univ Pompeu Fabra, IMIM Inst Hosp del Mar Invest Med, DCEXS,Hosp del Mar,Neurovasc Res Grp,Dept Neurol, Barcelona, Spain
Gomez-Gonzalez, A:
Univ Autonoma Barcelona, Univ Pompeu Fabra, IMIM Inst Hosp del Mar Invest Med, DCEXS,Hosp del Mar,Neurovasc Res Grp,Dept Neurol, Barcelona, Spain
Fernandez-Sanles, A:
IMIM Hosp del Mar Med Res Inst, Cardiovasc Epidemiol & Genet Res Grp, Barcelona, Spain
Elosua, R:
IMIM Hosp del Mar Med Res Inst, Cardiovasc Epidemiol & Genet Res Grp, Barcelona, Spain
CIBER Enfermedades Cardiovasc, Barcelona, Spain
Univ Vic Cent Univ Catalonia UVic UCC, Med Sch, Med Dept, Vic, Spain
Fernandez-Cadenas, I:
Inst Recerca Hosp Santa Creu & St Pau, Stroke Pharmacogen & Genet Grp, Barcelona, Spain
Cullell, N:
Inst Recerca Hosp Santa Creu & St Pau, Stroke Pharmacogen & Genet Grp, Barcelona, Spain
Hosp Univ MutuaTerrassa, Fundacio Docencia & Recerca MutuaTerrassa, Neurol, Terrassa, Spain
Montaner, J:
Univ Autonoma Barcelona, VHIR, Neurovasc Res Lab, Terrassa, Spain
Univ Seville, CSIC, Hosp Univ Virgen del Rocio, Inst Biomed Seville,IBiS, Seville, Spain
Hosp Univ Virgen Macarena, Dept Neurol, Seville, Spain
Moran, S:
Bellvitge Biomed Res Inst IDIBELL, Canc Epigenet & Biol Program PEBC, Barcelona, Spain
Esteller, M:
Josep Carreras Leukaemia Res Inst IJC, Barcelona, Spain
Ctr Invest Biomed Red Canc CIBERONC, Madrid, Spain
ICREA, Barcelona, Spain
UB, Sch Med & Hlth Sci, Physiol Sci Dept, Barcelona, Spain
Jimenez-Conde, J:
Univ Autonoma Barcelona, Univ Pompeu Fabra, IMIM Inst Hosp del Mar Invest Med, DCEXS,Hosp del Mar,Neurovasc Res Grp,Dept Neurol, Barcelona, Spain
Green Published
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