Sökning: onr:"swepub:oai:gup.ub.gu.se/144734" > Genome-wide associa...
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000 | 04707naa a2200721 4500 | |
001 | oai:gup.ub.gu.se/144734 | |
003 | SwePub | |
008 | 240910s2011 | |||||||||||000 ||eng| | |
024 | 7 | a https://gup.ub.gu.se/publication/1447342 URI |
024 | 7 | a https://doi.org/10.1371/journal.pgen.10013242 DOI |
040 | a (SwePub)gu | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Speliotes, Elizabeth K4 aut |
245 | 1 0 | a Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. |
264 | c 2011-03-10 | |
264 | 1 | b Public Library of Science (PLoS),c 2011 |
520 | a Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (∼26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n=880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ∼2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits. | |
700 | 1 | a Yerges-Armstrong, Laura M4 aut |
700 | 1 | a Wu, Jun4 aut |
700 | 1 | a Hernaez, Ruben4 aut |
700 | 1 | a Kim, Lauren J4 aut |
700 | 1 | a Palmer, Cameron D4 aut |
700 | 1 | a Gudnason, Vilmundur4 aut |
700 | 1 | a Eiriksdottir, Gudny4 aut |
700 | 1 | a Garcia, Melissa E4 aut |
700 | 1 | a Launer, Lenore J4 aut |
700 | 1 | a Nalls, Michael A4 aut |
700 | 1 | a Clark, Jeanne M4 aut |
700 | 1 | a Mitchell, Braxton D4 aut |
700 | 1 | a Shuldiner, Alan R4 aut |
700 | 1 | a Butler, Johannah L4 aut |
700 | 1 | a Tomas, Marta4 aut |
700 | 1 | a Hoffmann, Udo4 aut |
700 | 1 | a Hwang, Shih-Jen4 aut |
700 | 1 | a Massaro, Joseph M4 aut |
700 | 1 | a O'Donnell, Christopher J4 aut |
700 | 1 | a Sahani, Dushyant V4 aut |
700 | 1 | a Salomaa, Veikko4 aut |
700 | 1 | a Schadt, Eric E4 aut |
700 | 1 | a Schwartz, Stephen M4 aut |
700 | 1 | a Siscovick, David S4 aut |
700 | 1 | a NASH Clinical Research Network, (NASH CRN)4 aut |
700 | 1 | a Giant, Consortium4 aut |
700 | 1 | a MAGIC, Investigators4 aut |
700 | 1 | a Voight, Benjamin F4 aut |
700 | 1 | a Carr, J Jeffrey4 aut |
700 | 1 | a Feitosa, Mary F4 aut |
700 | 1 | a Harris, Tamara B4 aut |
700 | 1 | a Fox, Caroline S4 aut |
700 | 1 | a Smith, Albert V4 aut |
700 | 1 | a Kao, W H Linda4 aut |
700 | 1 | a Hirschhorn, Joel N4 aut |
700 | 1 | a Borecki, Ingrid B4 aut |
700 | 1 | a GOLD, Consortium4 aut |
700 | 1 | a Jansson, John-Olov,d 1954u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology4 aut0 (Swepub:gu)xjanjo |
710 | 2 | a Göteborgs universitetb Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi4 org |
773 | 0 | t PLoS geneticsd : Public Library of Science (PLoS)g 7:3q 7:3x 1553-7404 |
856 | 4 | u https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1001324&type=printable |
856 | 4 8 | u https://gup.ub.gu.se/publication/144734 |
856 | 4 8 | u https://doi.org/10.1371/journal.pgen.1001324 |
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