Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study.

Sayols, Sergi; Subirana Cachinero, Isaac; Lluís Ganella, Carla, 1984-; Civeira, Fernando; Roquer, Jaume; Do, AN; Absher, Devin; Cenarro, A.; Muñoz, Daniel; Soriano Tarraga, Carolina; Jiménez Conde, Jordi; Ordovás, José M.; Sentí Clapés, Mariano; Aslibekyan, Stella W.; Marrugat de la Iglesia, Jaume; Arnett, Donna K.; Elosua Llanos, Roberto

Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study.

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dc.contributor.author Sayols, Sergica
dc.contributor.author Subirana Cachinero, Isaacca
dc.contributor.author Lluís Ganella, Carla, 1984-ca
dc.contributor.author Civeira, Fernandoca
dc.contributor.author Roquer, Jaumeca
dc.contributor.author Do, ANca
dc.contributor.author Absher, Devinca
dc.contributor.author Cenarro, A.ca
dc.contributor.author Muñoz, Danielca
dc.contributor.author Soriano Tarraga, Carolinaca
dc.contributor.author Jiménez Conde, Jordica
dc.contributor.author Ordovás, José M.ca
dc.contributor.author Sentí Clapés, Marianoca
dc.contributor.author Aslibekyan, Stella W.ca
dc.contributor.author Marrugat de la Iglesia, Jaumeca
dc.contributor.author Arnett, Donna K.ca
dc.contributor.author Elosua Llanos, Robertoca
dc.date.accessioned 2017-02-24T09:22:48Z
dc.date.available 2017-02-24T09:22:48Z
dc.date.issued 2016
dc.description.abstract Lipid traits (total, low-densityand high-density lipoproteincholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is an inherited but also modifiable epigenetic mark that has been related tocardiovascular risk factors. Our aim was to identify loci showing differential DNA methylation related to serum lipid levels. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. Atwo-stage epigenome-wide association study was performed, with a discovery sample intheREGICOR study (n=645)and validation in the Framingham Offspring Study (n=2,542).FourteenCpG sites located in 9 genes (SREBF1, SREBF2, PHOSPHO1, SYNGAP1, ABCG1, CPT1A, MYLIP, TXNIP andSLC7A11) and 2 intergenic regions showeddifferential methylation in association with lipid traits. Six of these genes and 1 intergenic region were new discoveries showing differential methylation relatedto total cholesterol (SREBF2), HDL-cholesterol (PHOSPHO1, SYNGAP1 and an intergenic region in chromosome 2) and triglycerides (MYLIP, TXNIP andSLC7A11).These CpGs explained0.7%, 9.5% and18.9% of the variability of total cholesterol, HDL cholesterol and triglycerides in the Framingham Offspring Study, respectively. The expression of the genesSREBF2and SREBF1was inversely associated with methylation of their corresponding CpGs(p-value=0.0042 and 0.0045, respectively) in participants of the GOLDN study(n=98). In turn, SREBF1expression wasdirectly associated with HDL cholesterol(p-value=0.0429). Genetic variants in SREBF1, PHOSPHO1, ABCG1and CPT1Awerealso associated with lipid profile. Further research is warranted to functionally validatethesenew loci and assess the causality ofnew and established associationsbetween these differentially methylated lociand lipid metabolism.ca
dc.description.sponsorship This work was supported by the following sources: Agència de Gestio Ajuts Universitaris de Recerca [2014 SGR 240]; the Spanish Ministry of Economy through the Carlos III Health Institute [ISCIII-FIS-FEDER-ERDF PI12-00232, PI12-01238, PI11-01801, PI08-1327, PI05-1251, PI05-1297, PI02-0471, FIS99/0013-01, FIS96/0026-01, FIS93/0568, FIS92/0009-05], and the Red de Investigacion Cardiovascular [RD12/0042/0013, RD12/0042/0020, RD12/0042/0055, RD12/0042/0061]. S.S-B. was funded by a contract from Instituto de Salud Carlos III FEDER [IFI14/00007] and Daniel Bravo Andreu Private Foundation. GOLDN: The GOLDN study (AND, DA, JO, SA, DKA) was funded by the US National Institute of Health (NIH)/National Heart, Lung and Blood Institutes (http://www.nhlbi.nih.gov) grants R01HL104135 and U01HL72524.
dc.format.mimetype application/pdfca
dc.identifier.citation Sayols-Baixeras S, Subirana I, Lluis-Ganella C, Civeira F, Roquer J, Do AN. et. dentification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study. Hum Mol Genet. 2016 Oct 15;25(20):4556-4565. doi: 10.1093/hmg/ddw285ca
dc.identifier.doi http://dx.doi.org/10.1093/hmg/ddw285
dc.identifier.issn 0964-6906
dc.identifier.uri http://hdl.handle.net/10230/28137
dc.language.iso engca
dc.publisher Oxford University Pressca
dc.relation.ispartof Human Molecular Genetics. 2016 Oct 15;25(20):4556-65
dc.rights © Oxford University Press. This is a pre-copy-editing, author-produced PDF of an article accepted for publication inHuman Molecular Genetics following peer review. The definitive publisher-authenticated version Sayols-Baixeras S, Subirana I, Lluis-Ganella C, Civeira F, Roquer J, Do AN. et. dentification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study. Hum Mol Genet. 2016 Oct 15;25(20):4556-4565 is available online at: http://dx.doi.org/10.1093/hmg/ddw285ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.subject.other Epigènesica
dc.subject.other ADNca
dc.title Identification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study.ca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/acceptedVersionca

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