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Sökning: WFRF:(Carr R.) > (2010-2014) > Genome-wide associa...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004707naa a2200721 4500
001oai:gup.ub.gu.se/144734
003SwePub
008240910s2011 | |||||||||||000 ||eng|
0247 a https://gup.ub.gu.se/publication/1447342 URI
0247 a https://doi.org/10.1371/journal.pgen.10013242 DOI
040 a (SwePub)gu
041 a eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Speliotes, Elizabeth K4 aut
2451 0a 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 1b 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.
7001 a Yerges-Armstrong, Laura M4 aut
7001 a Wu, Jun4 aut
7001 a Hernaez, Ruben4 aut
7001 a Kim, Lauren J4 aut
7001 a Palmer, Cameron D4 aut
7001 a Gudnason, Vilmundur4 aut
7001 a Eiriksdottir, Gudny4 aut
7001 a Garcia, Melissa E4 aut
7001 a Launer, Lenore J4 aut
7001 a Nalls, Michael A4 aut
7001 a Clark, Jeanne M4 aut
7001 a Mitchell, Braxton D4 aut
7001 a Shuldiner, Alan R4 aut
7001 a Butler, Johannah L4 aut
7001 a Tomas, Marta4 aut
7001 a Hoffmann, Udo4 aut
7001 a Hwang, Shih-Jen4 aut
7001 a Massaro, Joseph M4 aut
7001 a O'Donnell, Christopher J4 aut
7001 a Sahani, Dushyant V4 aut
7001 a Salomaa, Veikko4 aut
7001 a Schadt, Eric E4 aut
7001 a Schwartz, Stephen M4 aut
7001 a Siscovick, David S4 aut
7001 a NASH Clinical Research Network, (NASH CRN)4 aut
7001 a Giant, Consortium4 aut
7001 a MAGIC, Investigators4 aut
7001 a Voight, Benjamin F4 aut
7001 a Carr, J Jeffrey4 aut
7001 a Feitosa, Mary F4 aut
7001 a Harris, Tamara B4 aut
7001 a Fox, Caroline S4 aut
7001 a Smith, Albert V4 aut
7001 a Kao, W H Linda4 aut
7001 a Hirschhorn, Joel N4 aut
7001 a Borecki, Ingrid B4 aut
7001 a GOLD, Consortium4 aut
7001 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
7102 a Göteborgs universitetb Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi4 org
7730 t PLoS geneticsd : Public Library of Science (PLoS)g 7:3q 7:3x 1553-7404
8564 u https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1001324&type=printable
8564 8u https://gup.ub.gu.se/publication/144734
8564 8u https://doi.org/10.1371/journal.pgen.1001324

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