000070598 001__ 70598 000070598 005__ 20200221144340.0 000070598 0247_ $$2doi$$a10.1093/hmg/ddw285 000070598 0248_ $$2sideral$$a106062 000070598 037__ $$aART-2016-106062 000070598 041__ $$aeng 000070598 100__ $$aSayols-Baixeras, S. 000070598 245__ $$aIdentification and validation of seven new loci showing differential DNA methylation related to serum lipid profile: an epigenome-wide approach. The REGICOR study 000070598 260__ $$c2016 000070598 5060_ $$aAccess copy available to the general public$$fUnrestricted 000070598 5203_ $$aLipid traits (total, low-density and high-density lipoprotein cholesterol, and triglycerides) are risk factors for cardiovascular disease. DNA methylation is not only an inherited but also modifiable epigenetic mark that has been related to cardiovascular 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 Human Methylation 450 BeadChip. A two-stage epigenome-wide association study was performed, with a discovery sample in the REGICOR study (n = 645) and validation in the Framingham Offspring Study (n = 2, 542). Fourteen CpG sites located in nine genes (SREBF1, SREBF2, PHOSPHO1, SYNGAP1, ABCG1, CPT1A, MYLIP, TXNIP and SLC7A11) and 2 intergenic regions showed differential methylation in association with lipid traits. Six of these genes and 1 intergenic region were new discoveries showing differential methylation related to total cholesterol (SREBF2), HDLcholesterol (PHOSPHO1, SYNGAP1 and an intergenic region in chromosome 2) and triglycerides (MYLIP, TXNIP and SLC7A11). These CpGs explained 0.7%, 9.5% and 18.9% of the variability of total cholesterol, HDL cholesterol and triglycerides in the Framingham Offspring Study, respectively. The expression of the genes SREBF2 and SREBF1 was 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, SREBF1 expression was directly associated with HDL cholesterol ( P-value = 0.0429). Genetic variants in SREBF1, PHOSPHO1, ABCG1 and CPT1A were also associated with lipid profile. Further research is warranted to functionally validate these new loci and assess the causality of new and established associations between these differentially methylated loci and lipid metabolism. 000070598 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/FIS92-0009-05$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/FIS93-0568$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/FIS96-0026-01$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/FIS99-0013-01$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI02-0471$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI05-1251$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI05-1297$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI08-1327$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI11-01801$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI12-00232$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI12-01238 000070598 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/ 000070598 590__ $$a5.34$$b2016 000070598 591__ $$aGENETICS & HEREDITY$$b23 / 166 = 0.139$$c2016$$dQ1$$eT1 000070598 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b46 / 287 = 0.16$$c2016$$dQ1$$eT1 000070598 592__ $$a3.698$$b2016 000070598 593__ $$aGenetics$$c2016$$dQ1 000070598 593__ $$aMolecular Biology$$c2016$$dQ1 000070598 593__ $$aMedicine (miscellaneous)$$c2016$$dQ1 000070598 593__ $$aGenetics (clinical)$$c2016$$dQ1 000070598 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000070598 700__ $$aSubirana, I. 000070598 700__ $$aLluis-Ganella, C. 000070598 700__ $$0(orcid)0000-0001-7043-0952$$aCiveira, F.$$uUniversidad de Zaragoza 000070598 700__ $$aRoquer, J. 000070598 700__ $$aDo, A.N. 000070598 700__ $$aAbsher, D. 000070598 700__ $$aCenarro, A. 000070598 700__ $$aMunoz, D. 000070598 700__ $$aSoriano-Tarraga, C. 000070598 700__ $$aJimenez-Conde, J. 000070598 700__ $$aOrdovas, J.M. 000070598 700__ $$aSenti, M. 000070598 700__ $$aAslibekyan, S. 000070598 700__ $$aMarrugat, J. 000070598 700__ $$aArnett, D.K. 000070598 700__ $$aElosua, R. 000070598 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina 000070598 773__ $$g25, 20 (2016), 4556-4565$$pHum. mol. genet.$$tHUMAN MOLECULAR GENETICS$$x0964-6906 000070598 8564_ $$s254900$$uhttps://zaguan.unizar.es/record/70598/files/texto_completo.pdf$$yVersión publicada 000070598 8564_ $$s102918$$uhttps://zaguan.unizar.es/record/70598/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000070598 909CO $$ooai:zaguan.unizar.es:70598$$particulos$$pdriver 000070598 951__ $$a2020-02-21-13:49:56 000070598 980__ $$aARTICLE