000131475 001__ 131475
000131475 005__ 20240319081030.0
000131475 0247_ $$2doi$$a10.1016/j.ajhg.2022.06.012
000131475 0248_ $$2sideral$$a136849
000131475 037__ $$aART-2022-136849
000131475 041__ $$aeng
000131475 100__ $$aRamdas, S.
000131475 245__ $$aA multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
000131475 260__ $$c2022
000131475 5203_ $$aA major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
000131475 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000131475 590__ $$a9.8$$b2022
000131475 591__ $$aGENETICS & HEREDITY$$b11 / 171 = 0.064$$c2022$$dQ1$$eT1
000131475 592__ $$a4.943$$b2022
000131475 593__ $$aGenetics (clinical)$$c2022$$dQ1
000131475 593__ $$aGenetics$$c2022$$dQ1
000131475 594__ $$a17.2$$b2022
000131475 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000131475 700__ $$aJudd, J.
000131475 700__ $$a. Graham,S
000131475 700__ $$aKanoni,S.
000131475 700__ $$aWang,
000131475 700__ $$aSurakka,I
000131475 700__ $$aWenz,B.
000131475 700__ $$aClarke, SL
000131475 700__ $$aChesi, A.
000131475 700__ $$aWells, A.
000131475 700__ $$a. Bhatti, K. F
000131475 700__ $$aVedantam, S. Winkler,
000131475 700__ $$aT. W.
000131475 700__ $$aLocke, A. E.
000131475 700__ $$aMarouli, E.
000131475 700__ $$aZajac, G.
000131475 700__ $$aWu,K. H.
000131475 700__ $$aNtalla, Q. Hui
000131475 700__ $$aKlarin, D.
000131475 700__ $$aHilliard,A. T.
000131475 700__ $$aWang, Z.
000131475 700__ $$aXue, C.
000131475 700__ $$aThorleifsson, G.
000131475 700__ $$aHelgadottir, A.
000131475 700__ $$aGudbjartsson, DF.
000131475 700__ $$aHolm, H.
000131475 700__ $$aOlafsson, I
000131475 700__ $$aHwang, M.
000131475 700__ $$aHan, S.
000131475 700__ $$aAkiyama, M.
000131475 700__ $$aSakaue, S.
000131475 700__ $$aTerao, C.
000131475 700__ $$aKanai, M.
000131475 700__ $$aZhou, W.
000131475 700__ $$aBrumpton, B. M.
000131475 700__ $$aRasheed, H.
000131475 700__ $$aHavulinna, A. S.
000131475 700__ $$aVeturi, Y.
000131475 700__ $$aPacheco, J. A.
000131475 700__ $$aRosenthal, E. A.
000131475 700__ $$aLingren, T.
000131475 700__ $$aFeng, Q.
000131475 700__ $$aKullo, I. J.
000131475 700__ $$aNarita, A.
000131475 700__ $$aTakayama, J.
000131475 700__ $$aMartin, H. C.
000131475 700__ $$aHunt, K. A
000131475 700__ $$aTrivedi, B.
000131475 700__ $$aHaessler, J.
000131475 700__ $$aGiulianini, F.
000131475 700__ $$aBradford, Y.
000131475 700__ $$aMiller, JE
000131475 700__ $$aCampbell, A.
000131475 700__ $$aLin, K.
000131475 700__ $$aMillwood, IY
000131475 700__ $$aRasheed, A.
000131475 700__ $$aHindy, G.
000131475 700__ $$aFaul, JD.
000131475 700__ $$aZhao, W.
000131475 700__ $$aWeir, DR
000131475 700__ $$aTurman, C.
000131475 700__ $$aHuang, H.
000131475 700__ $$aGraff, M
000131475 700__ $$aChoudhury, A
000131475 700__ $$aSengupta, D.
000131475 700__ $$aMahajan, A.
000131475 700__ $$aBrown, MR
000131475 700__ $$aZhang, W.
000131475 700__ $$aYu, K.
000131475 700__ $$aSchmidt, EM
000131475 700__ $$aPandit, A.
000131475 700__ $$aGustafsson, S.
000131475 700__ $$aYin, X
000131475 700__ $$aLuan, J.
000131475 700__ $$aZhao, J.
000131475 700__ $$aMatsuda, J.
000131475 700__ $$aJang, H.
000131475 700__ $$aYoon, H.
000131475 700__ $$aMedina-Gomez, C.
000131475 700__ $$aPitsillides, A
000131475 700__ $$aHottenga, JJ.
000131475 700__ $$aWood, AR
000131475 700__ $$aJi, Y.
000131475 700__ $$aGao, Z.
000131475 700__ $$aHaworth, S.
000131475 700__ $$aMitchell, E.
000131475 700__ $$aChai, JF
000131475 700__ $$aAadahl, M.
000131475 700__ $$aBjerregaard, AA.
000131475 700__ $$aYao, J.
000131475 700__ $$aManichaikul, A.
000131475 700__ $$aChao, A.
000131475 700__ $$aWarren, H.R.
000131475 700__ $$0(orcid)0000-0003-4130-5866$$aRamírez, J.$$uUniversidad de Zaragoza
000131475 700__ $$aet al.
000131475 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000131475 773__ $$g109, 8 (2022), 1366-1387$$pAm. j. hum. genet.$$tAMERICAN JOURNAL OF HUMAN GENETICS$$x0002-9297
000131475 8564_ $$s2300460$$uhttps://zaguan.unizar.es/record/131475/files/texto_completo.pdf$$yVersión publicada
000131475 8564_ $$s734800$$uhttps://zaguan.unizar.es/record/131475/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000131475 909CO $$ooai:zaguan.unizar.es:131475$$particulos$$pdriver
000131475 951__ $$a2024-03-18-17:06:40
000131475 980__ $$aARTICLE