Journal article
Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits
EK Speliotes, LM Yerges-Armstrong, J Wu, R Hernaez, LJ Kim, CD Palmer, V Gudnason, G Eiriksdottir, ME Garcia, LJ Launer, MA Nalls, JM Clark, BD Mitchell, AR Shuldiner, JL Butler, M Tomas, U Hoffmann, SJ Hwang, JM Massaro, CJ O'Donnell Show all
Plos Genetics | PUBLIC LIBRARY SCIENCE | Published : 2011
Open access
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 (~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 ..
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Funding Acknowledgements
This work was partially supported by NIH grants T32 DK07191-32 to Daniel Podolsky (for EKS), F32 DK079466-01 to EKS, NIH K23DK080145-01 to EKS, and R01DK075787 to JNH. The AGES-Reykjavik Study is funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The Old Order Amish Study was supported by NIH research grants K01 DK067207, R01 AG18728, R01HL088119, U01 HL72515, and U01 HL084756. Partial funding was also provided by the Diabetes Research and Training Center of Maryland (P60 DK079637) and the Nutrition and Obesity Research Center of Maryland (P30DK072488). LMY-A was supported by NIH training grants T32AG000262 and F32AR059469. RH was supported by the American Diabetes Association Mentor-Based Postdoctoral Fellowship Program (7-07-MN-08). The NHLBI Family Heart Study was supported by NIDDK R01DK075681 (to IBB) and NHLBI R01HL087700. This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix for genotyping services (Contract No. N02-HL-6-4278). The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713). Several clinical centers use support from General Clinical Research Centers or Clinical and Translational Science Awards in conduct of NASH CRN Studies (grants UL1RR024989, M01RR000750, M01RR00188, ULRR02413101, M01RR000827, UL1RR02501401, M01RR000065, M01RR020359). The MIGen study was funded by the US National Institutes of Health (NIH) and National Heart, Lung, and Blood Institute's STAMPEED genomics research program. MT was supported by the Beatriu de Pinos postdoctoral fellowship, Generalitat de Catalunya (2007BP-B100068, MT), and Red HERACLES, ISCIII (RD06/0009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.