Search: (WFRF:(Marten A)) srt2:(2020-2022) pers:(Li M.) >
A multi-layer funct...
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Ramdas, S.Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA,University of Pennsylvania
(author)
A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- Article/chapterEnglish2022
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LIBRIS-ID:oai:gup.ub.gu.se/318991
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https://gup.ub.gu.se/publication/318991URI
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https://doi.org/10.1016/j.ajhg.2022.06.012DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-485348URI
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https://lup.lub.lu.se/record/18eea727-15e8-44ae-8089-2f683de2fa23URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:150690307URI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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For complete list of authors see http://dx.doi.org/10.1016/j.ajhg.2022.06.012De fem första författarna delar förstaförfattarskapet.
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A 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.
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Judd, J.
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Graham, S. E.
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Kanoni, S.
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Wang, Y. X.
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Surakka, I.
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Wenz, B.
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Lind, LarsKarolinska Institutet,Uppsala universitet,Klinisk epidemiologi(Swepub:uu)larslind
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Chesi, A.
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Wells, A.
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Martin, H. C.
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Kurbasic, A.Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)mats-aku
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Trivedi, B.
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Gustafsson, StefanUppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi(Swepub:uu)stegu732
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Mellström, Dan,1945Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition(Swepub:gu)xmelda
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Stefansson, K.
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Zhang, J. F.
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Chen, Y. E.
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Ho, Y. L.
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Lynch, J. A.
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Tsao, P. S.
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Chang, K. M.
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Cho, K.
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O'Donnell, C. J.
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Gaziano, J. M.
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Wilson, P.
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Mohlke, K. L.
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Frayling, T. M.
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Hirschhorn, J. N ...
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Kathiresan, S.
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Boehnke, M.
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Grant, S.
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Natarajan, P.
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Sun, Y. V.
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Morris, A. P.
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Deloukas, P.
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Peloso, G.
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Assimes, T. L.
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Willer, C. J.
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Zhu, X.
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Brown, C. D.
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Genetics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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American Journal ...
- By the university
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University of Gothenburg
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Uppsala University
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Lund University
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Karolinska Institutet