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Public Library of Science, PLoS Genetics, 3(7), p. e1001324, 2011

DOI: 10.1371/journal.pgen.1001324

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Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits

Journal article published in 2011 by Elizabeth K. Speliotes, Laura M. Yerges-armstrong, M. Yeh, A. Ünalp, K. Yates, Jian Yang, J. H. Zhao, S. van Wingerden, M. den Heijer, J. B. J. van Meurs, G.-J. van Ommen, J. Xu, Q. Zhang, L. Zgaga, A. Ziegler and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

Abstract

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 ( approximately 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 approximately 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